瑞舒伐他汀通过丝裂原活化蛋白激酶p38信号通路对大鼠心肌缺血再灌注损伤的保护作用

Protective effect of rosuvastatin on myocardial ischemia-reperfusion injury in rats via mitogen-activated protein kinase p38 signaling pathway

目的探究瑞舒伐他汀(RSV)通过丝裂原活化蛋白激酶p38(p38MAPK)信号通路对大鼠心肌缺血再灌注损伤(MIRI)的保护作用。方法将SD大鼠随机分为对照组、模型组和高、低剂量实验组,每组各15只。建模前7 d,高、低剂量实验组分别灌胃给予20、5 mg·kg^(-1)·d^(-1)RSV,对照组和模型组均灌胃给予等量0.9%NaCl。4组大鼠每天早晚各给药1次,连续给药7 d后,对照组仅开胸后缝合,不作其余处理,其余3组大鼠均用结扎冠状动脉左前降支的方法建立MIRI模型。用双染色方法检测心肌缺血程度,用全自动酶标仪检测血清一氧化氮(NO)、内皮素(ET)、血管细胞黏附因子-1(VCAM-1)和内皮细胞间黏附分子-1(ICAM-1)水平,用蛋白质印迹法检测心脏组织中p38MAPK和生长抑素受体1(SSTR1)蛋白的表达水平。结果低、高剂量实验组和模型组、对照组的心肌缺血程度分别为(36.26±0.38)%、(30.53±0.31)%、(42.60±0.44)%和0,NO水平分别为(25.41±2.67)、(32.81±3.36)、(19.07±2.01)和(39.86±4.13)μmol·L^(-1),ET水平分别为(170.28±17.07)、(157.39±15.25)、(191.75±20.55)和(132.26±14.61)mmol·L^(-1),VCAM-1水平分别为(234.09±23.56)、(218.73±21.71)、(252.35±25.39)和(200.62±20.06)pg·mL^(-1),ICAM-1水平分别为(24.89±0.26)、(20.73±0.22)、(30.89±0.34)和(14.82±0.16)pg·mL^(-1),磷酸化p38MAPK/p38MAPK蛋白比值分别为0.57±0.06、0.41±0.40、0.80±0.08和0.32±0.04,SSTR1蛋白相对表达水平分别为1.02±0.11、0.95±0.10、1.20±0.13和0.41±0.05。高、低剂量实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论RSV对大鼠MIRI具有一定的保护作用,其机制可能与p38MAPK信号通路有关。

Objective To investigate the protective effect of rosuvastatin(RSV)on myocardial ischemia-reperfusion injury(MIRI)in rats through mitogen activated protein kinase p38(p38MAPK)signaling pathway.Methods SD rats were randomly divided into control group,model group and experimental-L,-H groups with 15 rats per group.Seven days before modeling,the experimental-L,-H groups were given 20 mg·kg^(-1)·d^(-1)RSV intragastrically,and the control and model groups were given 0.9%NaCl intragastrically,respectively.Four groups were administrated once each morning and evening.After continuous administration for 7 days,the control group was sutured after thoracotomy without any other treatment,the MIRI model rats were established by ligating the left anterior descending branch of coronary artery in the other three groups.The degree of myocardial ischemia was detected by double-staining method.The serum levels of nitric oxide(NO),endothelin(ET),vascular cell adhesion factor-1(VCAM-1)and interendothelial cell adhesion molecule-1(ICAM-1)were detected by automatic enzyme marker.The expression levels of p38MAPK and somatostatin receptor 1(SSTR1)protein were detected by Western blot.Results The degrees of myocardial ischemia in experimental-L,experimental-H,model and control groups were(36.26±0.38)%,(30.53±0.31)%and(42.60±0.44)%and 0;NO levels were(25.41±2.67),(32.81±3.36),(19.07±2.01)and(39.86±4.13)μmol·L^(-1);ET levels were(170.28±17.07),(157.39±15.25),(191.75±20.55)and(132.26±14.61)mmol·L^(-1);VCAM-1 levels were(234.09±23.56),(218.73±21.71),(252.35±25.39)and(200.62±20.06)pg·mL^(-1);ICAM-1 levels were(24.89±0.26),(20.73±0.22),(30.89±0.34)and(14.82±0.16)pg·mL^(-1);the phosphorylated p38MAPK/p38MAPK protein ratios were 0.57±0.06,0.41±0.40,0.80±0.08 and 0.32±0.04;the relative expression levels of SSTR1 protein were 1.02±0.11,0.95±0.10,1.20±0.13 and 0.41±0.05,respectively.Compared with the model group,the differences of above indexes in the experimental-L,-H groups were statistically significant(all P<0.05).Conclusion RSV has a protective effect on MIRI in rats,and its mechanism may be related to p38MAPK signaling pathway.