藻蓝蛋白对大鼠急性心肌缺血再灌注损伤的保护作用

Protective effects of phycocyanin on myocardium in rats with acute myocardial ischemia reperfusion injuries

目的观察藻蓝蛋白对大鼠急性心肌缺血再灌注损伤的保护作用。方法将48只SPF级SD大鼠左冠状动脉前降支用丝线结扎30 min后恢复灌注的方法建立急性心肌缺血再灌注损伤模型,术后随机分为模型对照组和藻蓝蛋白A、B组,另取8只不造模作为空白对照组。藻蓝蛋白A、B两组用藻蓝蛋白混悬液[100、400 mg/(kg·d)]灌胃给药治疗10 d,空白对照组和模型对照组等量生理盐水灌胃。检测静脉血总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性及大鼠左心室缺血区心肌组织丙二醛(MDA)含量,免疫组化技术检测各组大鼠心肌细胞内诱导型一氧化氮合酶(i NOS)的表达,图像分析法检测冠状动脉细胞周期蛋白依赖激酶抑制因子P21和P27的表达。结果经藻蓝蛋白治疗后,藻蓝蛋白A、B两组T-SOD和GSH-PX活性明显提高,MDA显著降低,冠状动脉P21和P27基因高表达,i NOS阳性细胞数明显减少,与模型组和本组成模后比较,差异均有统计学意义(P<0.05);藻蓝蛋白A、B组组间比较,差异无统计学意义(P>0.05)。结论藻蓝蛋白通过促进蛋白依赖激酶抑制因子P21和P27基因表达,提高T-SOD和GSH-PX酶活性,抑制缺血心肌产生i NOS及脂质过氧化反应对心肌细胞的破坏,降低心肌细胞病理性血管重构而达到心肌保护作用。

Objective To observe the protective effects of phycocyanin on myocardium in rats with acute myocardial ischemia reperfusion injuries （MIRI）, and explore the mechanism. Methods The model of acute myocardial ischemia reperfusion injury was established by ligating the left anterior descending coronary artery of 48 SPF SD rats with 30 rain after reperfusion, then they were divided into 3 groups： model control group, phycocyanin group A and group B, another 8 rats were selected as normal control group. Rats in phycoeyanin group A and group B were treated with phycoeyanin by intragastric administration [100, 400 mg/（kg.d）] for 10 d, rats in model control group and normal control group were treated with the same does of 0.9% sodium chloride solution by intragastric administration. The activity of T-SOD and GSH-PX were detected in the tail venous blood, the content of MDA in myocardium was detected, the expression of iNOS in cardiac myocytes was detected by immunohistochemistry. The expression of cyclin dependent kinase inhibitor P21 and P27 in coronary artery was detected by image analysis. Results Compared with model control group and after modelling, the activity of T-SOD and GSH-PX in group A and group B improved significantly, the content of MDA reduced significantly, the expression of cyclin dependent kinase inhibitor P21 and P27 in coronary artery improved significantly, the expression of iNOS in cardiac myocytes reduced significantly, the differences were statistically significant （P 〈 0.05）. Phycocyanin group A were compared with Phyeocyanin group B, the differences were not statistically significant （P 〉 0.05）. Conclusion Phycocyanin can protect myocardium with MIRI by promoting P21 and P27 gene expression, improving T-SOD and GSH-PX enzyme activity, controlling iNOS and lipid peroxidation of ischemic myocardium and reducing the myocardial cell pathological vascular remodeling.