SHAO Jin’gen,YANG Jiang,CHEN Haohao, et al. The effect of cerebral ischemia reperfusion in different time on autophagy of hippocampal neurons and PI3K/mTOR pathway in rats[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2020, 50(2): 102-107.
Abstract:Objective: To investigate the effect of cerebral ischemia reperfusion in different time on autophagy of hippocampal neurons and PI3K/mTOR pathway in rats. Methods: Totally 72 rats were randomly divided into sham operation group and cerebral ischemia reperfusion groups (reperfusion for 0 h, 6 h, 12 h, 24 h,
36 h, respectively), with 12 rats in each group. The rat model of global cerebral ischemia reperfusion injury was established by four-vessel occlusion. Modified neurological severity score was used to evaluate hippocampal neurological function in rats, HE staining was used to detect the damage of hippocampal neurons in rats, the autophagic bodies in hippocampal neurons were observed under transmission electron microscopy, Western blot was used to detect the expressions of Beclin-1, LC3 II, p62, p-PI3K, p-Akt, and p-mTOR proteins. Results: Compared with the sham operation group, the cerebral ischemia reperfusion rats showed an increase in the modified neurological severity score, cerebral infarction area, and the number of autophagosomes; the expressions of autophagy-related proteins Beclin-1 and LC3 II in hippocampus of rats were significantly up-regulated (P<0.05), the expression of p62 was significantly down-regulated (P<0.05), the expressions of PI3K/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR were significantly down-regulated (P<0.05). With the prolongation of cerebral ischemia reperfusion time, the expressions of autophagy-related proteins Beclin-1 and LC3 II increased, the expression of p62 decreased and so did the PI3K/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR. Conclusion: Cerebral ischemia reperfusion can enhance autophagy of hippocampal neurons and inhibit PI3K/mTOR signaling pathway in rats.
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