Effects of nimodipine on autophagy in rats with cerebral ischemia
LI Lubo1, CHEN Bo2, QIAN Yao1, LI Qiaoyu2
(1. School of Medicine, Jiangsu University,Zhenjiang Jiangsu 212013; 2. Department of Neurosurgery, the Affiliated People′s Hospital of Jiangsu University, Zhenjiang Jiangsu 212002, China)
Abstract:Objective: To study the effect of nimodipine on autophagy in rats with cerebral ischemia and its therapeutic effect. Methods: Ninety SD rats were randomly divided into nimodipine group, sham operation group, and middle cerebral artery focal line suture method(MCAO) model group(ischemic model group), 30 in each group. Experimental model rats were selected according to the ZeaLonga score.The MCAO rat model was prepared and the expression level of LC3Ⅱ, Beclin1, mTOR/pmTOR proteins were detected by Western blotting. The infarct volume of brain tissue was observed by TTC staining, and the damage of brain tissue was observed by HE staining. The astrocyte oxygen glucose deprivation(OGD) model was constructed, and the cells were divided into blank control group, OGD model group and nimodipine group. LC3Ⅱ, Beclin1, mTOR/pmTOR protein expression were determined by Western blotting; astrocyte activity was tested by CCK8 assay. Results: Compared with the sham operation group, the ischemic model group showed higher expression of LC3Ⅱ, Beclin1 and mTOR/pmTOR protein(P<0.05). Compared with the ischemic model group, the nimodipine group showed lower protein expression of LC3Ⅱ, Beclin1 and higher expression of mTOR(P<0.05), with decreased infarct volume of brain tissue and the number of cell death. In the OGD test, compared with the OGD model group, the cell activity in the nimodipine group was increased, and the expression of LC3Ⅱand Beclin1 protein was decreased significantly(P<0.05). Conclusion: Nimodipine could inhibit autophagy and reduce the damage of brain tissue in rats with cerebral ischemia.
[1]Donnan GA, Fisher M, Macleod M, et al. Stroke[J]. Lancet, 2008, 371(9624): 1612-1623.[2]Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation[J]. Science, 2000, 290(5497): 1717-1721.[3]Alirezaei M, Kemball CC, Flynn CT, et al. Shortterm fasting induces profound neuronal autophagy[J]. Autophagy, 2010, 6(6): 702-710.[4]Ecker N, Mor A, Journo D, et al. Induction of autophagic flux by amino acid deprivation is distinct from nitrogen starvationinduced macro autophagy[J]. Autophagy, 2010, 6(7): 879-890