Mitochondria are the main sites of aerobic respiration in living cells.normal mitochondrial function is the basis of maintaining metabolic energy supply and an indispensable part of immune signaling,while the homeostasis of autophagy is the cornerstone of maintaining Normal mitochondrial function^[9]。 Mitophagy is a selective autophagy process induced by external stimuli such as reactive oxygen species(ROS)stress,nutrient deficiency and cell aging,which induces the separation,closure and lysosomal degradation of phagocytic vesicles in the membrane.It can remove damaged or redundant mitochondria and maintain the balance between the number and quality of mitochondria,which is an important part of mitochondrial quality control and is closely related to the occurrence and development of neurodegenerative diseases,cancer,cardiovascular diseases and other diseases^[10][11]。 It has been confirmed that mitophagy is a dual-action process with complex mechanisms,which has both potential benefits and certain risks.Therefore,future research should focus on how to maximize its positive effects^[12]。 Bcl-2/adenovirus E1B-19 kDa interacting protein 3(BNIP3)and its analog(BNIP3-like protein X,NIX)and functional domain containing protein 1(FUNDC1)are the two most important receptors mediating mitophagy in mammalian physiological and pathological conditions.PINK1(phosphate and tension homology induced putative kinase 1)/PARKIN-E3 ubiquitin protein ligase(PARKIN)is currently recognized as a pathway involved in mitochondrial autophagosome formation,autophagy adaptor recruitment,and TANK-binding kinase 1-driven autophagy receptor phosphorylation(Figure 1)^[13]。

Macrophages,as the first line of defense of the innate immune system against pathogen exposure,can play a key host defense mechanism through phagocytosis,recruit other immune cells to the site of infection,activate the serum complement system and adaptive immune response,phagocytize and eliminate foreign pathogens,thus playing a role in immune regulation^[14-15]。 It is believed that non-polarized macrophages(M0 type)are mainly characterized by classical activated macrophages(M1 type)mediating proinflammatory response and alternative activated macrophages(M2 type)mediating anti-inflammatory response,in which M1 type macrophages are mainly induced by lipopolysaccharide(LPS)to secrete tumor necrosis factor(TNF).cytokines such as TNF-α,IL-1β,IL-6,IL-8 and IL-12,with CD80,CD86 and inducible nitric oxide synthase(iNOS)as the main surface markers,cause inflammatory response,phagocytize and kill pathogens.M2 macrophages are mainly induced by IL-4 to secrete Cytokines such as IL-10,transforming growth factor(TGF)-β,and vascular endothelial growth factor(VEGF),with CD206,CD163,and arginase(Arg)-1 as the main surface markers to reduce inflammation and promote tissue repair and regeneration(Figure 2)^[16]。 Studies have shown that macrophages can be divided into three functional subsets:host defense macrophages(similar to M1 type),wound healing macrophages(similar to M2 type)and immune regulatory macrophages(mediated by factors secreted by regulatory T cells,memory CD4⁺T cells,etc.).The same macrophage may have the characteristics of two subsets,and different functional subsets can be transformed into each other.The transformation of macrophage polarization state plays an important role in the immune response of pathogen infection,cancer,autoimmune diseases and other diseases^[17]。 At present,there are many studies on personalized macrophage targeting strategy in disease treatment^[18]。

Macrophages,as the sentinel cells of the innate immune system,originate from hematopoietic stem cells and are transformed from monocytes after entering damaged tissues.Macrophages are distributed in various target organs such as liver,heart,lung,spleen,kidney,brain,skin and vascular endothelium along with peripheral blood.It is responsible for the release of IL-1β,IL-6,IL-8,IL-12,IL-18,IL-33,TNF-α,granulocyte-macrophage colony-stimulating factor,macrophage migration inhibitory factor,monocyte chemoattractant protein-1(MCP-1),IL-1ra,TGF-β,prostaglandin E2 and other cellular inflammatory factors,as well as interferon,complement and other active substances,whose activation disorder can directly affect the outcome of sepsis^[19][20-21]。

In the early stage of sepsis,proinflammatory factors such as interferon-γ(IFN-γ)and LPS induce macrophages to polarize to M1 type and release a large number of inflammatory factors,such as IL-1,TNF-α,IL-6,ROS,iNOS,etc.,which cause a severe systemic inflammatory factor storm,damage the target organs of sepsis,and cause chain organ dysfunction^[22]。 Studies have found that when macrophages in sepsis are stimulated,the expression level of cytokine matrix metalloproteinase-9 is significantly increased,which is positively correlated with the severity of the disease^[23]。 TNF-αand IL-1βproduced by macrophages can activate neutrophils during sepsis,and polymorphonuclear neutrophils can secrete exosomal miR-30d-5p,which can induce cell apoptosis and histopathological changes by activating nuclear factor-κB(NF-κB)signaling pathway,and promote sepsis-related acute lung injury^[24]。 in addition,Toll-like receptor 4(TLR4)on the surface of macrophages can regulate the polarization of macrophages from M1 type to M2 type by mediating NF-κB and mitogen-activated protein kinase(MAPK)signaling pathways,maintain the balance of mitochondrial dynamics In tissues,reduce oxidative stress and apoptosis,and alleviate sepsis-induced myocardial injury^[25]。 In terms of therapy,previous studies have shown that targeting macrophages to deliver miR-21 to reprogram them(reduce M1 and activate M2),reduce the inflammatory regulation of macrophage phenotype,reverse myocardial remodeling and prevent vascular ischemia-reperfusion injury^[26]。 Inhibition of hexokinase 2 regulation of macrophage glycolysis by Kr Krüppel-like transcription factor 14 can also significantly reduce the level of inflammation in mice and improve the survival rate of septic mice^[27]。

On the contrary,in the late stage of sepsis,the secretion of M1 macrophages is reduced,the secretion of M2 macrophages is excessive,or the secretion of both M1 and M2 macrophages is inhibited,which induces the host to enter an immunosuppressive state,at which time the susceptibility of the body to opportunistic and nosocomial secondary infections is significantly increased^[28]。 In the sepsis mouse model established by cecal ligation and puncture,the turning point from severe inflammation to immunosuppression occurred within 24 hours after ligation^[29-30]。 Clinical observations showed that peripheral blood monocyte mitochondrial respiration was lower and systemic inflammatory response was higher in septic children with immune paralysis than in those without immune paralysis^[31]。 Serum ferritin and human leukocyte antigen-DR(HLA-DR)/CD14 were measured in 240 Patients with sepsis caused by pulmonary infection,bacteremia,or acute cholangitis in a double-blind,randomized,controlled clinical study.patients with immune paralysis had a higher mortality rate than those without immune paralysis^[32]。

mitochondria,as the main provider of polarization energy for macrophages,produce ATP for cell metabolism When they function normally.when it is destroyed by injury,ROS are produced,initiating mitochondrial autophagy.Mitophagy is a self-protective measure,which can eliminate damaged mitochondria,prevent protein accumulation,inhibit ROS production,maintain the quantity and quality of mitochondria,and maintain the normal physiological function of cells^[33]。 However,when the degree of mitophagy is too high,it will lead to excessive elimination of mitochondria,resulting in mitochondrial deficiency and behavioral disorders,such as anxiety-like and depression-like behavior^[34]。 Mitochondrial autophagy has been widely studied in the regulation of macrophage polarization^[35-36]。 Accumulating evidence suggests that mitophagy plays a key role in the regulation of inflammatory signaling and is expected to be a therapeutic target for innate immunity in sepsis infection^[37]。

It Has been shown that deletion of endosomal adaptor protein APPL1 inhibits mitophagy,resulting in the accumulation of damaged mitochondria,the production of ROS and oxidized membrane mitochondrial deoxyribonucleic acid,and the initiation of nucleotide-binding oligome rization domain-like receptor protein 3 in macrophages.Excessive activation of NLRP3 inflammasome enhances the activity of systemic cysteinyl aspartate specific protease(Caspase-1)and the production and secretion of IL-1β,which is an important mechanism of endotoxin-induced inflammatory cytokine storm in sepsis^[35]。 in a mouse model of LPS-induced sepsis,specific overexpression of Beclin-1,a key regulatory protein complex of autophagy,can promote mitophagy by inhibiting the release of mitochondrial damage-related molecular patterns and activating PINK1/PARKIN signaling pathway.It can reduce the uncontrolled infection and excessive inflammation caused by LPS-induced M1 macrophage polarization,and improve myocardial fibrosis and cardiac function In septic mice,while inhibiting mitophagy has the opposite effect^[38-39]。 Ubiquitin-specific protease 19 can inhibit NLRP3 inflammasome activation by increasing autophagic flux and reducing mitochondrial ROS production,which in turn promotes M2 macrophage polarization and is a potential therapeutic target for inflammatory intervention^[40]。

Other studies have shown that Inhibition of mitophagy is a physiological mechanism that helps to activate myeloid cells and improve the prognosis of sepsis.inhibition of mitophagy by PINK1-deficient bone marrow or drugs promotes macrophage activation,which is conducive to bacterial clearance and survival.Switching to mitochondrial uncouplers,which promote mitophagy,reverses LPS/IFN-γ-mediated macrophage activation,resulting in immune paralysis,impaired bacterial clearance,and reduced survival^[36]。

It can be seen that the regulation of the relationship between mitophagy and macrophage polarization is essential for the treatment of sepsis,but the timing of intervention in Western medicine is controversial,because there may be dynamic positive and negative two-way regulation between the two.the concept of"preventive treatment of disease"and the mechanism of"two-way regulation"of traditional Chinese medicine are particularly critical at this time。

With the development of traditional Chinese medicine(TCM)research,the separation and extraction technology of TCM has been greatly developed,which has realized the preparation and analysis of effective,non-toxic,consistent and stable monomer components of TCM,and researchers have paid more and more attention to various extracts of TCM decoction pieces^[48]。

triptolide plays an anti-inflammatory role in promoting mitophagy and macrophage polarization to M2 type.Through the interaction between autophagy and apoptosis,Triptolide increases the expression of acidic vacuoles,light chain 3(LC3)and autophagy-related gene(ATG)proteins,and stimulates ROS production.It activates the Caspase family of enzymes involved in programmed cell death(especially apoptosis),increases mitochondrial membrane potential(MMP),enhances phagocytosis of T cells,B cells,monocytes,and macrophages,and exerts anti-inflammatory,anti-proliferative,pro-apoptotic,and immune-enhancing functions^[49]。 Quercetin,as a natural polyphenol flavonoid,can inhibit the activation of NLRP3 inflammasome in microglia mediated by excessive ROS by promoting mitophagy,and prevent neuronal damage^[50]。 Similarly,baicalin can significantly down-regulate the levels of LC3Ⅱ/Ⅰ,p62 and translocase 20,up-regulate the levels of NIX,AMP-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),improve mitochondrial autophagy in hippocampal neurons,and reduce depressive-like behavior in mice^[51]。 Ginseng root extract induced autophagy through protein kinase B(Akt)-mammalian target of rapamycin(mTOR)signaling pathway,alleviated excessive oxidation,mitochondrial dysfunction and inflammation,enhanced the expression of Beclin-1,LC3Ⅱand ATG7 proteins,significantly inhibited the injury of LPS-induced colitis,and played a similar role as NF-κB and N-terminal kinase inhibitors^[52]。

In terms of inhibiting mitophagy,maintaining M1 macrophage secretion and enhancing immunity,some studies have pointed out that C21steroid glycoside is the main active component of Euphorbia pekinensis,which initiates mitophagy-dependent apoptosis by inducing mitochondrial dysfunction and ROS accumulation.It can inhibit ATP1A1-Akt/extracellular signal-regulated kinase(ERK)signaling pathway,regulate the release of inflammatory cytokines,promote M2 macrophage polarization,enhance phagocytosis,kill pathogens,and has a significant effect on viral infections,cancer,leukemia,convulsions and so on^[53-54]。 In addition,as the main fat-soluble extract of Salvia miltiorrhiza,cryptotanshinone has antitumor,antioxidant,anti-inflammatory,antibacterial and other activities,which can be used as an antitumor immunomodulator through apoptosis signal-regulated kinase 1(ASK1).ASK1)pathway inhibits mitochondrial oxidative phosphorylation and fusion,inhibits M2-type macrophage differentiation,and triggers autoubiquitination-dependent activation of TNF receptor-associated factor 6 of ASK1,promotes ubiquitination and degradation of ASK1,and helps to convert tumor-associated macrophages to M1-type,leading to tumor regression^[55][47]。

Many traditional Chinese medicine extracts have also shown good effects in the two-way regulation of mitophagy and macrophage polarization.Paeoniflorin,as a water-soluble monoterpene glycoside,has concentration-and function-dependent bidirectional immunomodulatory effects.On the one hand,it can repair damaged mitochondria by increasing MMP and reducing ROS accumulation;On the other hand,renal tissue was protected from inflammatory injury by up-regulating the expression of PINK1,PARKIN,BNIP3,p62 and Kr Krüppel-like transcription factor 4,inhibiting the infiltration of M1-type macrophage markers(CD68,iNOS,IL-6,IL-1β,TNF-α,MCP-1,etc.)and increasing the proportion of M2-type macrophage markers(CD206,Arg1,FIZZ1,IL-10 and Ym-1,etc.)^[46]。 Puerarin can also regulate mitophagy in both directions.On the one hand,it can reverse the decrease of mitochondrial enzyme activity,adenosine monophosphate,adenosine diphosphate and ATP levels caused by LPS by regulating dynamin-related protein 1(Drp1)and mitomycin 1,mediate p62,LC3B,PINK1 and PARKIN to promote mitophagy in H9C2 cells,and prevent sepsis from adversely affecting the cardiovascular system^[56]。 At the same time,it can inhibit FUNDC1-mediated mitophagy by activating PI3K-Akt-mTOR signaling pathway,reversing MMP levels and ATP content,and protecting cells from oxidative damage similar to mitochondrial fission inhibitor Mdivi^[57]。

In addition,recent studies have found that many traditional Chinese medicine extracts,such as Artemisia annua leaf extract,gypenoside,notoginsenoside R1,fisetin,pseudoephedrine and emodin,can significantly improve mitochondrial metabolic function by regulating autophagy pathway.Regulate the polarization state of macrophages,remove cytotoxic substances,alleviate the inflammatory reaction and immunosuppression caused by sepsis,protect nerves,vascular endothelium and tissues,effectively antagonize the immune disorder of sepsis,and inhibit the damage of sepsis to organs^{[58][59][60][61][62]}。

Traditional Chinese medicine compound takes"monarch,minister,assistant and guide"as the main compatibility principle,according to the individual condition of patients,from the overall perspective to achieve the effect of treating the same disease differently and treating different diseases with the same treatment^[63]。

for the syndrome of excessive toxic heat in sepsis,Gegen Qinlian Decoction(Radix Puerariae,Radix Scutellariae,Rhizoma Coptidis,and Radix Glycyrrhizae)can play its role as a classic prescription For exogenous exterior syndrome and heat sinking in Yangming,relieving exterior syndrome and clearing interior syndrome,resisting inflammation and bacteria,reducing blood sugar and lipid,and resisting oxidation^[64]; Wang et al observed that the expression of mitophagy proteins(such as PINK,PARKIN,LC3B,p62,BNIP3,FUNDC1,Beclin-1,inhibin 2 and mitofusin 1)was significantly increased,while the expression of phosphorylated Drp1 was significantly decreased in mice with nonalcoholic fatty liver disease after taking Gegen Qinlian Decoction^[65]。 in addition,the expression of macrophage infiltration markers(F4/80,CD11b)and M1 macrophage polarization markers(CD11c,CCR7)decreased,the expression of M2 macrophage polarization markers(CD163,CD206)increased,the ratio of M2/M1 increased,and the proinflammatory cytokines and NLRP3 inflammasome decreased significantly.Liangge Powder(Radix et Rhizoma Rhei,Fructus Forsythiae,Radix Scutellariae,Herba Menthae,Fructus Gardeniae,Mirabilitum,and Radix Glycyrrhizae)is the best choice for patients with Yangming Fu-organ excess,which is especially good at clearing stagnant heat In the upper and middle energizer,purging fire,detoxifying,and relaxing the bowels,and can down-regulate glycogen synthase kinase(GSK),a characteristic gene related to inflammatory chemotactic pathway.the expression of GSK-3βmRNA promotes the phosphorylation and inactivation of GSK-3β,induces the polarization of M1 macrophages to M2 macrophages,and reduces neutrophil infiltration and inflammatory injury of the body,which is a promising candidate for the treatment of sepsis^[66]。

Daming capsule(Radix et Rhizoma Rhei,Semen Cassiae,Radix Salviae Miltiorrhizae,Pericarpium Citri Reticulatae,Radix Ginseng,and Poria)and Taohong Siwu Decoction(Semen Persicae,Flos Carthami,Radix Rehmanniae Preparata,Radix Angelicae Sinensis,Rhizoma Chuanxiong,and Radix Paeoniae)are commonly used to cope with sepsis with blood stasis syndrome.the Daming Capsule has the effects of clearing heat and reducing turbidity,promoting blood circulation and removing blood stasis,can Increase the expression of mitochondrial autophagic receptor nucleotide binding oligomerization domain-like receptor X1,reduce the colocalization of mitochondria and lysosomes and MMP,increase the accumulation of mitochondrial ROS,activate the silent information regulator/AMPK signaling pathway,inhibit the inflammatory response and oxidative stress of cardiomyocytes,reduce cardiomyocyte apoptosis,and improve cardiac function^[67]。 Taohong Siwu Decoction can protect PC12 cells from OGD reperfusion injury and improve cell survival rate by enhancing mitophagy and inhibiting the activation of NLRP3 inflammasome^[68]。

Buyang Huanwu Decoction(Radix Astragali,Radix Angelicae Sinensis,Radix Paeoniae Rubra,Rhizoma Chuanxiong,Semen Persicae,Flos Carthami,and Pheretima)has the effects of invigorating qi,promoting blood circulation,and dredging collaterals for acute deficiency syndrome caused by immunosuppression in the late stage of sepsis.High dose(20 mg/kg)can significantly reduce myocardial apoptosis,alleviate inflammatory microenvironment,and improve the survival rate of septic mice by inhibiting CD45 immune cell infiltration.Paeoniflorin and calycosin,the key molecules,can inhibit NF-κB signaling pathway,up-regulate TGF-βpathway,inhibit local macrophage aggregation and immune cell infiltration,promote M2 macrophage polarization,and alleviate myocardial injury in sepsis^[69]。 The formula for supplementing qi and invigorating the spleen(Radix Astragali,Radix Pseudostellariae,Radix Angelicae Sinensis,Fructus Ligustri Lucidi,Poria,Rhizoma Atractylodis Macrocephalae,Pericarpium Citri Reticulatae,Radix Scutellariae,and Radix Glycyrrhizae)focuses on invigorating the spleen and replenishing qi and nourishing qi and blood,can improve the number of peripheral blood lymphocytes and the proportion of CD8⁺T lymphocytes in the rat model of acute and chronic liver failure,and increase proinflammatory factors(IL-2,Reduce anti-inflammatory factors(IL-10 and TGF-β1),improve the metabolism and mitochondrial balance of CD8⁺T lymphocytes,alleviate lymphocyte immune dysfunction by promoting autophagy,promote the expression of PGC-1α,nuclear respiratory transcription factor 1 and mitochondrial transcription factor A,regulate the relationship between autophagy and mitochondrial biogenesis,improve immunosuppression,and promote the balance of immune response^[70]。

Dachengqi Decoction(Radix et Rhizoma Rhei,Fructus Aurantii Immaturus,Cortex Magnoliae Officinalis,and Natrii Sulfas)can be the first choice for the syndrome of fu-organ qi obstruction,and its main ingredients,such as luteolin,aloe-emodin,and naringenin,can promote the expression of vitamin D receptor.reduce the apoptosis of lung tissue or alveolar macrophages and the activation of NLRP3 inflammasome in LPS-induced sepsis-related acute lung injury mice,increase the expression of autophagic proteins such as ATG16L1 and Beclin1,enhance their autophagic response,and Reduce the inflammatory level of alveolar macrophages^[41][71][72]。 For multiple organ dysfunction in mice with gut-derived sepsis,Dachengqi Decoction could significantly reduce the sepsis score and the levels of TNF-αand IL-6,and improve the 7-day survival rate by inhibiting systemic inflammation and apoptosis,and down-regulating TLR4/myeloid differentiation factor 88(MyD88)signaling pathway^[73][74]。

Acupuncture and moxibustion,with its characteristics of"simplicity,convenience,cheapness and effectiveness",is widely used in the treatment of many diseases,including improving blood circulation,promoting metabolism,regulating immune function and relieving pain^[75⇓-77]。 the scientificity of its meridian theory has been constantly confirmed,and The selectivity,regional specificity,neuroanatomical basis,stimulation intensity and acupuncture depth of acupoints have become research hotspots^[78][79]。 Studies have shown that electrical stimulation(ES)drives the sympathetic pathway in a somatic and intensity-dependent manner,and low-intensity ES activates the vagus-adrenal axis in the hindlimb region,resulting in an anti-inflammatory effect dependent on neuropeptide Y⁺of adrenal chromaffin cells.High-intensity ES activates neuropeptide Y⁺splenic noradrenergic neurons in the abdomen via the spinal sympathetic axis,which participates in a feed-forward regulatory loop and produces anti-inflammatory or pro-inflammatory effects^[80]。

in terms of sepsis immunomodulation,combined treatment with Sanyinjiao and indomethacin reduced inflammatory cell infiltration,vascular permeability,and myeloperoxidase activity In LPS-exposed rats^[81]。 the previous study of our research group also found that"intestinal three needles"including Zusanli,Tianshu and Shangjuxu acupoints could significantly increase the diversity of intestinal flora and the content of beneficial flora in septic rats,reduce intestinal bacterial translocation and reduce inflammatory response by regulating the transient receptor potential vanilloid subtype 1/calcitonin gene-related peptide signaling pathway^[82]。 Zusanli(ST 36)is an empirical acupoint for improving the immune function of sepsis,which has the effects of anti-inflammation,enhancing immunity,anti-oxidation,and accelerating the recovery of gastrointestinal diseases,and can significantly reduce the expression of TLR4 and NF-κB.It upregulates the infiltration of CD3⁺,CD4⁺and CD8⁺lymphocytes,restores the CD4⁺/CD8⁺ratio,controls systemic inflammation through vagus nerve activation,has obvious curative effect on heart,lung,kidney,brain and other organ injuries in sepsis,and significantly improves the survival rate of septic animals^[83]。 Electroacupuncture pretreatment at Hegu point significantly attenuated the systemic inflammatory response in rats with lethal sepsis by activating muscarinic receptors in the central nervous system,increasing the survival rate from 20%to 80%,and is expected to become a preventive treatment for sepsis or perioperative diseases associated with excessive inflammation^[84]。 Tianshu acupoint has a significant effect on improving gastrointestinal function in patients with sepsis,and the intestinal immune barrier plays a key role in regulating innate and adaptive immune responses,so it is speculated that the overall immunomodulatory effect of Tianshu acupoint may be achieved by improving gastrointestinal function and thus enhancing the intestinal immune barrier^[85][86]。 Geshu acupoint can inhibit TLR4/MyD88 signaling pathway through ES and alleviate cognitive impairment related to immune inflammation^[87]。 ES can also increase the levels of monocyte HLA-DR and T cell subsets(CD3⁺,CD4⁺,CD8⁺,CD4⁺/CD8⁺)in septic patients,and produce analgesia,which may be related to the recruitment of neutrophils to releaseβ-endorphin,or to the inhibition of the expression of adiponectin receptor interfering RNA in the spinal cord by adiponectin/adiponectin receptor 2-mediated AMPK pathway^[88][89][90]。 In addition,ES has a good targeting effect on anxiety and depression,and has a significant effect on autoimmune diseases such as multiple sclerosis and immune enteritis,which can reduce recurrence,regulate immune barrier and improve quality of life^{[91][92][93][94]}。

in terms of mitophagy,electroacupuncture significantly increased MMP and ATP In patients with cerebral ischemia-reperfusion,improved mitochondrial function,reduced neuronal damage,and protected neurons from cerebral ischemia-reperfusion injury by removing nitro or oxidative stress-induced mitochondrial function damage through PINK1/PARKIN-mediated mitophagy^[95]。 Electroacupuncture can increase the expression of schizophrenia-related gene 1,promote mitophagy,enhance the clearance ofβ-amyloid protein,reduce the cytotoxicity of hippocampal neurons,and improve the learning and memory function of diabetic rats^[96]。 EA pretreatment can also protect myocardium from myocardial ischemia-reperfusion injury by inhibiting apoptosis and mitophagy mediated by mTORC1/Unc-51-like kinase 1/FUNDC1 signaling pathway,and reduce ventricular arrhythmia score and the levels of creatine kinase isoenzyme MB,lactate dehydrogenase,and cardiac-specific troponin T^[97]。