阿托伐他汀对局灶性脑缺血大鼠脑组织中自噬及血管新生的影响

Effect of atorvastatin on autophagy and angiogenesis in brain tissue of focal cerebral ischemia rats

目的:观察阿托伐他汀对局灶性脑缺血大鼠脑组织中自噬及血管新生的影响。方法:雄性SD大鼠63只,随机分为假手术组、模型组、他汀组,每组21只。模型组和他汀组采用大脑中动脉栓塞法造模,假手术组不栓塞。术前1周,他汀组给予阿托伐他汀钙片4 mg/(kg·d)灌胃,其余两组给予等量生理盐水灌胃。术后24 h处死大鼠,TTC染色观察脑梗死面积,免疫组化法检测脑组织中CD105、IRE1的表达,RT-PCR检测血管内皮细胞生长因子(VEGF)mRNA,Western blot法检测自噬蛋白LC3-Ⅱ。结果:与假手术组相比,模型组及他汀组脑组织皮层及皮层下有明显梗死灶,缺血半暗带区CD105、IRE1、VEGF mRNA、LC3-Ⅱ表达升高(P<0.05);他汀组上述变化较模型组更显著(P<0.05)。模型组、他汀组脑组织中VEGF mRNA与LC3-Ⅱ表达有明显线性正相关关系(r=0.837、0.850,P均<0.05)。结论:阿托伐他汀可通过增强自噬,促进局灶性脑缺血血管新生。

Aim： To observe the effect of atorvastatin on autophagy and angiogenesis in brain tissue of focal cerebral ischemia rats. Methods： A total of 63 male SD rats were randomly allocated into sham operation group,model group and treatment group,and each group contained 21 rats. One week before surgery,the treatment group received a gavage of atorvastatin at 4 mg /（ kg·d）,and the other 2 groups were given the same amount of normal saline. All rats were killed 24 h after operation. The area of cerebral infarction was measured by TTC staining. The expressions of CD105 and IRE1 protein in brain tissue were detected by immunohistochemistry. The expression of VEGF mRNA was detected by RT-PCR. The expression of LC3-Ⅱprotein was detected by Western blot. Results： Compared with those of sham operation group,the cortex and subcortical brain tissue of model group and treatment group showed obvious infarction. The expressions of CD105,IRE1,VEGF mRNA and LC3-Ⅱ in ischemic penumbra area in model group and treatment group were higher. Compared with those of the model group,the indexes mentioned above in treatment group were much higher（ P〈0. 05）. In model group and treatment group,the expression of LC3-Ⅱand that of VEGF mRNA had positive linear relationship（ r = 0. 837,0. 850,P〈0. 05）. Conclusion：Atorvastatin can promote angiogenesis in focal cerebral ischemia tissue by enhancing autophagy.