姜黄素对小鼠脑缺血再灌注的脑组织中NO含量和Bcl-2、Bax表达的影响

目的通过观察姜黄素对脑缺血再灌注小鼠脑组织中NO含量及Bcl-2、Bax蛋白表达的影响,探讨姜黄素对缺血性脑损伤的神经保护作用及机制。方法 180只雄性健康昆明种小鼠,随机分为A(假手术组)、B(溶剂对照组)和C(姜黄素治疗组)。各组于缺血再灌注后分为3、6、24、48和72 h 5个亚组。采用线栓法建立小鼠局灶性脑缺血再灌注模型。各组于24 h后进行小鼠神经功能学评分:HE染色后于光学显微镜下观察组织学变化;用硝酸还原酶法测定脑组织中NO含量;应用免疫组织化学法检测Bcl-2、Bax蛋白表达水平。结果 24 h神经功能评分B组明显高于A组,C组与B组相比差,异有统计学意义(P0.05)。NO含量B组与A组相比,3、6、24 h差异有统计学意义(P0.05)。C组与B组比较,6、24 h差异有统计学意义(P0.05)。B组随时间延长脑组织中Bcl-2、Bax的表达增加,Bcl-2/Bax的比值下降;C组Bcl-2表达显著增加,降低了Bax的表达。结论姜黄素对脑缺血再灌注性脑损伤具有保护作用,其作用机制可能与降低NO含量及提高Bcl-2蛋白表达水平、抑制Bax蛋白表达减少细胞凋亡来减少脑缺血后迟发性神经元损伤有关。

Effects of curcumin on NO content and expression of Bcl-2 and Bax in brain tissue of mice with cerebral ischemia and reperfusion injury

[Objective]To study the neuroprotective effects and mechanism of curcumin on mice with cerebral ischemia and reperfusion by analyzing the changes of NO content,Bcl-2 and Bax protein.[Methods]Kunming male healthy mice(n=180) were divided into sham-operated group(group A),Solvent control group(group B),curcumin treatment group(group C) randomly.After ischemia and reperfusion,all groups were divided into 3 h,6 h,24 h,48 h and 72 h subgroups.The mouse models of focal cerebral ischemia and reperfusion were established by suture method.The neurological score of each group was estimated at 24 h.The histopathologic changes were observed by the HE staining method.The NO level wasdetected by the method of nitric acid reductase.Immunochemistry was used to evaluate the expression level of Bcl-2,Bax.[Results]The neurological score in group B was significantly higher than that of group A.While in group C it was significantly different with group B(P<0.05).The content of NO was significantly different between group A and B group at 3 h,6 h and 24 h(P<0.05).While there were significant differences between C group and B group at 6 h and 24 h(P<0.05).The Bcl-2 and Bax expression were increased,while Bcl-2/Bax was decreased in group B.In group C,Bcl-2 expression was obviously increased,and Bax expression was reduced.[Conclusion]Curcumin has neuroprotective effect on mice with cerebral ischemia and reperfusion.Its mechanism might be that the decreasing of expression of NO content and Bax increasing results in inhibition of Bax protein expression and decreased apoptosis and then lead to reduction of delayed neuronal damage after cerebral ischemia.