miRNA-29c在大鼠脑缺血再灌注神经损伤中的保护作用与机制

目的探讨miRNA-29c在大鼠脑缺血再灌注神经损伤中的保护作用与机制研究。方法 48只雄性SD大鼠随机分为假手术组,模型组,miR-29c NC组,miR-29c inhibitor组,除假手术组外,其余三组均采用拴线法建立大鼠大脑中动脉局灶缺血再灌注损伤模型,并于术后24 h评价大鼠神经行为变化,检测大鼠脑梗死体积,缺血侧脑组织细胞凋亡情况,脑组织中miR-29c表达量,超氧化物岐化酶(SOD)活性,丙二醛(MDA)含量,含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase 3),Caspase 8及Caspase 9活性,及Bcl-2,Bax,Bak1,cleaved caspase 3,cleaved caspase 8与cleaved caspase 9蛋白表达。结果与假手术组比较,模型组,miR-29c NC组中miR-29c表达量显著提高,大鼠神经行为评分提高,脑梗死体积增加,细胞凋亡率提高,SOD活性降低,MDA含量,Caspase 3,Caspase 8及Caspase 9活性上升,Bcl-2表达量下调,Bax,Bak1,cleaved caspase 3,cleaved caspase 8及cleaved caspase 9表达量上调,差异均具有统计学意义(P0.01)。与模型组及miR-29c NC组比较,miR-29c inhibitor组miR-29c表达量显著降低,大鼠神经行为评分降低,脑梗死体积百分比减少,细胞凋亡率降低,SOD活性上升,MDA含量,Caspase 3,Caspase 8及Caspase 9活性降低,Bcl-2表达量上调,Bax,Bak1,cleaved caspase 3,cleaved caspase 8及cleaved caspase9表达量下调,差异均具有统计学意义(P0.01)。结论 miR-29c对大鼠脑缺血再灌注神经损伤具有保护作用,与提高抗氧化能力及调控细胞凋亡相关蛋白表达有关。

The mechanism and protective effect of miR-29c on cerebral ischemia-reperfusion injury in rats

Obejective To explore protective effect of miR-29c on cerebral ischemia-reperfusion injury in rats. Methods Forty eight SD rats were randomly divided into sham group, model group, miR-29c NC group and miR-29c inhibitor group. Except the sham operation group, the other three groups were established by using ligation of middle cerebral artery. Twenty four hours after the operation, neurological behavior score, cerebral infarction volume, cell apoptosis, the activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), cysteine aspartic acid protease 3 (caspase 3), caspase 8, caspase 9, and the expression of miR-29c, Bcl-2, Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9. Results Compared with sham group, neurological behavior score, cerebral infarction volume, cell apoptosis rate was increased, SOD th the expression of miR-29c, activity was decreased, the level of MDA, caspase 3, caspase 8 and caspase 9 activity was increased. The expression of Bcl-2 was down-regulated, the expression of Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9 expression was up-regulated in model group, miR-29c NC group. The differences were also statistically significant (P<0.01). Compared with model group, miR-29c NC group, the expression of miR-29c, neurological behavior score, cerebral infarction volume percentage, cell apoptosis rate was decreased, SOD activity was increased, the level of MDA, caspase 3, caspase 8 and caspase 9 activity was decreased. The expression of Bcl-2 was up-regulated, the expression of Bax, Bak1, cleaved caspase 3, cleaved caspase 8 and cleaved caspase 9 expression was down-regulated in miR-29c inhibitor group. The differences were also statistically significant (P<0.01). Conclusion miR-29c had a protective effect on cerebral ischemia-reperfusion injury in rats, which was related to improve the antioxidant capacity and regulation of apoptosis related protein expression.