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Research on effect and possible mechanisms of cutting formula of pantao pills on cognitive impairment in spontaneously hypertensive rats
GUOManping, SHIWeili, ZHAOJunnan, XINQiqi, XUFengqin, CONGWeihong, CHENKeji
Chinese Journal of Alzheimer's Disease and Related Disorders ›› 2019, Vol. 2 ›› Issue (3) : 408-415.
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Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders
Editor in chief: Jun WANG
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Research on effect and possible mechanisms of cutting formula of pantao pills on cognitive impairment in spontaneously hypertensive rats
Objective: To observe the effects of the cutting formula of Pantao Pills on the cognitive function of spontaneously hypertensive rats (SHRs), and the possible mechanism. Methods: Wistar kyoto (WKY) rats were used as control group. SHR were randomly divided into model group, irbesartan+donepezil group, donepezil group, low-dose group of the cutting formula of Pantao Pills 3.07 g/(kg·d) and high-dose group of the cutting formula of Pantao Pills 6.14 g/(kg·d). Twelve rats in each group, half male and half female, were given orally once a day for 11 weeks. After 11 weeks of administration, cognitive memory function was examined by Morris water maze; morphological changes of brain tissue were observed by hematoxylin-eosin (HE) staining; serum renin (REN) levels were measured by ELISA, and aldosterone (ALD) and angiotensin Ⅱ (Ang II) levels were measured by radioimmunoassay. Western Blot method was used to analyze phosphoinositide 3-kinase (PI3K), phosp-horylated-PI3K (p-PI3K), protein kinase B (AKT), p-AKT, extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, p38 mitogen-activated protein kinase (p38 MAPK), p-p38 MAPK protein expression level in brain. Results: Compared with the control group, the swimming distance of SHR model group was significantly longer; the cortex and hippocampus of SHR model rats were loose, the density of neurons was decreased, and there were more vacuoles and cell fragments, the levels of PI3K, p-AKT and AKT protein in brain tissue of SHR model group were significantly lower, while the levels of p-p38 MAPK protein were significantly higher; compared with SHR model group, the swimming distance of SHRs in the water maze positioning and navigation test was significantly shortened in the high dose group (P=0.01) and the low dose group (P=0.003) of the cutting formula of Pantao Pills, the high dose group and the low dose group of the cutting formula of Pantao Pills significantly reduced neuronal damage and nuclear cohesion in cortex and hippocampus, decreased the pathological changes of hippocampus and cortical neurons; the high dose group of the cutting formula of Pantao Pills can up-regulate the level of brain PI3K (7^=0.021), p-AKT (P=0.000), AKT (7^=0.001) protein, down-regulate the level of brain p-p38 MAPK (P=0.001), p38 MAPK (P=0.008) protein. Conclusion: This suggests that the cutting formula of Pantao Pills can improve the cognitive impairment of SHRs and protect neurons. The mechanism may be related to the regulation of PI3K/AKT, p-AKT, AKT, p-p38 MAPK and other related proteins in brain PI3K/AKT and p38 MAPK signaling pathways of SHRs.
The cutting formula of Pantao Pills / Cognitive impairment / SHRs / PI3K/AKT / MAPK
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