Expression of mTOR/autophagy pathway in the hippocampus following cerebral ischemia/reperfusion injure in intermittent hypoxia rats

Abstract

Objective: To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion, so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia. Methods: One hundred healthy male Wistar rats were randomly divided into: sham operation group(SO group, n=20), intermittent hypoxia group(IH group, n=20), merely ischemia/reperfusion group(I/R group, n=20), intermittent hypoxia ischemia/reperfusion group(IH+ I/R group, n=20), intermittent hypoxia ischemia/reperfusion+ mTOR inhibitor group(Inhibitor group, n=20). IH group, IH+ I/R group and inhibitor group were respectively given intermittent hypoxia for 21 days before ischemia/reperfusion. Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO), the morphological changes of hippocampus nerve cells of rat brain were detected with HE respectively 6, 24 h after ischemia, and the expressions of mTOR protein and beclin1 protein in hippocampus of rat brain was detected with immunohistochemistry and RT-PCR respectively 6, 24 h after ischemia.SPSS 17.0 software was used to analyze the data. Results: Compared with the SO group, the IH group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 32.94, 47.31, 63.68, 78.45, all P<0.05); the I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (mTOR in I/R group: 22.38±0.46, 24.16±0.60; mTOR in SO group: 14.65±0.48, 15.40±0.58; beclin1 in I/R group: 8.58±0.58, 10.58±0.49; beclin1 in SO group: 2.06±0.23, 2.10±0.30; the differences were significant, q value was 90.59, 106.83, 95.88, 119.44, all P<0.05). Compared with the IH group, IH+ I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 152.23, 165.61, 135.01, 156.48, all P<0.05). Compared with the I/R group, IH+ I/R group increased the never cells morphology damages and the empression of mTOR and beclin1(q value was 94.35, 106.99, 102.79, 115.49, all P<0.05). Compared with the IH+ I/R group, the inhibitor group decreased the never cells morphology damages and the expression of mTOR, increased the expression of beclin1(mTOR in IH+ I/R group: 30.40±0.43, 32.86±0.50; mTOR in inhibitor group: 26.60±0.37, 28.51±0.52; beclin1 in IH+ I/R group: 15.57±0.57, 18.78±0.43; beclin1 in inhibitor group: 21.74±0.51, 24.32±0.49; the differences were significant, q value was 44.71, 53.05, 90.74, 78.03, all P<0.05). Conclusion: Intermittent hypoxia can aggravate the damage on nerve cells by activating mTOR/autophagy pathway after ischemia.