title: [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 (qvalue was 32.94, 47.31, 63.68, 78.45, allP<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,qvalue was 90.59, 106.83, 95.88, 119.44, allP<0.05). Compared with the IH group, IH+ I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (qvalue was 152.23, 165.61, 135.01, 156.48, allP<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(qvalue was 94.35, 106.99, 102.79, 115.49, allP<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,qvalue was 44.71, 53.05, 90.74, 78.03, allP<0.05).Conclusion:Intermittent hypoxia can aggravate the damage on nerve cells by activating mTOR/autophagy pathway after ischemia.
authors.affiliation: College of Nursing and Rehabilitation in North China University of Science and Technology.
authors.forename: X F
authors.initials: XF
authors.lastname: Guo
authors.affiliation: College of Nursing and Rehabilitation in North China University of Science and Technology; Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Y N
authors.initials: YN
authors.lastname: Zhao
authors.affiliation: College of Nursing and Rehabilitation in North China University of Science and Technology; Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China.
authors.forename: J M
authors.initials: JM
authors.lastname: Li
authors.affiliation: College of Nursing and Rehabilitation in North China University of Science and Technology.
authors.forename: C X
authors.initials: CX
authors.lastname: Chen
authors.affiliation: College of Nursing and Rehabilitation in North China University of Science and Technology.
authors.forename: S X
authors.initials: SX
authors.lastname: Li
mesh_terms: D000818:Animals; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000071186:Beclin-1; C512829:Becn1 protein, rat; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases