尼莫地平对脑缺血大鼠自噬的影响

目的: 研究尼莫地平对大鼠脑缺血自噬的影响及治疗作用。方法: 将90只SD大鼠随机均分为大脑中动脉局灶性线栓法(MCAO)模型组(缺血模型组)、尼莫地平组、假手术组,每组30只。根据Zea Longa评分选取实验用模型鼠。制备MCAO大鼠模型,采用蛋白质印迹法检测LC3 Ⅱ、Beclin 1、m TOR／p mTOR蛋白表达。应用TTC染色观察脑组织梗死体积,HE染色观察脑组织细胞损伤状况。制备星形胶质细胞氧糖剥夺(OGD)模型,将细胞分为空白对照组、OGD模型组、尼莫地平组,采用蛋白质印迹法检测LC3 Ⅱ、Beclin 1、m TOR／p mTOR蛋白,CCK8实验检验星形胶质细胞活性。结果： 与假手术组相比,缺血模型组LC3 Ⅱ、Beclin 1蛋白以及m TOR／p mTOR蛋白表达明显增加(P均<0.05)。与缺血模型组相比,尼莫地平组LC3 Ⅱ、Beclin 1蛋白表达明显降低,m TOR蛋白表达明显增加(P<0.05),脑组织梗死体积和细胞死亡数明显降低(P均<0.05)。在OGD试验中,与OGD模型组相比,尼莫地平组细胞活性升高,LC3 Ⅱ、Beclin 1蛋白表达降低(P<0.05)。 结论： 尼莫地平可抑制脑缺血大鼠自噬发生,降低自噬对脑组织的损伤。

Effects of nimodipine on autophagy in rats with cerebral ischemia

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 Zea Longa score.The MCAO rat model was prepared and the expression level of LC3 Ⅱ, Beclin 1, m TOR／p mTOR 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. LC3 Ⅱ, Beclin 1, m TOR／p mTOR 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 LC3 Ⅱ, Beclin 1 and m TOR／p mTOR protein(P<0.05). Compared with the ischemic model group, the nimodipine group showed lower protein expression of LC3 Ⅱ, Beclin 1 and higher expression of m TOR(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 LC3 Ⅱand Beclin 1 protein was decreased significantly(P<0.05). Conclusion: Nimodipine could inhibit autophagy and reduce the damage of brain tissue in rats with cerebral ischemia.