丹酚酸B对心肌梗死模型大鼠心肌的保护作用及其分子机制

目的：观察丹酚酸B（Sal B）对心肌梗死模型大鼠心肌的保护作用，阐明Sal B干预大鼠心肌梗死的分子机制。方法：将大鼠随机分为对照组、模型组、阳性药实验组（AsA组和BHT组）和观察药实验组（Sal B组），采用冠状动脉结扎法构建大鼠心肌梗死模型。各实验组大鼠均按120 mg/kg剂量腹腔注射给药，模型组与对照组大鼠注射相同剂量的蒸馏水，连续7 d。测定各组大鼠血清中肌酸磷酸激酶（CK）、天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）的活性，并利用ELISA法分析各组大鼠血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达水平；流式细胞术检测各组大鼠心肌细胞凋亡率，分光光度法检测自由基清除率。结果：与对照组比较，模型组大鼠血清CK、AST和LDH活性明显升高（P<0.01）;与模型组比较，阳性药实验组和Sal B组大鼠血清CK、AST和LDH活性明显降低（P<0.05或P<0.01）。与对照组比较，模型组大鼠血清中IL-1β、IL-6、TNF-α水平明显增加（P<0.01）；与模型组比较，Sal B组大鼠血清中IL-1β、IL-6和TNF-α水平显著降低（P<0.01）；而AsA和BHT组上述3种因子水平无明显变化（P>0.05）。与对照组比较，模型组大鼠心肌细胞凋亡率明显增加（P<0.01）；与模型组比较，Sal B组大鼠心肌细胞凋亡率明显降低（P<0.01）；而AsA和BHT组大鼠心肌细胞凋亡率无明显改变(P>0.05)。不同浓度的Sal B均能提高1,1-二苯基-2-三硝基苯肼（DPPH）自由基的清除率（P<0.05），且20～100 mg/L Sal B对自由基的清除率均高于AsA和BHT（P<0.05或P<0.01）。结论：Sal B对大鼠冠状动脉结扎诱发实验性心肌梗死具有一定的保护作用，可以有效抑制心肌细胞凋亡，其作用机制可能与抑制免疫炎症因子的分泌和自由基清除作用有关。

Protective effect of salvianolic acid B on myocardium of myocardial infarction model rats and its molecular mechanism

Objective To investigate the protective effect of salvianolic acid B(Sal B) on myocardium of myocardial infarction model rats and to clarify the molecular mechanism of Sal B intervention in myocardial infarction.Methods The SD rats were randomly divided into control group,model group,positive drug experiment(AsA and BHT) groups and observation drug experiment group(Sal B group).The myocardial infarction models of rats were set up by coronary artery ligation.The rats in every experiment groups were administered by intraperitoneal injection with the dose of 120 mg·kg-1,the rats in model group and control group were injected with the same dose of distilled water for 7 d.Then the activities of CK,AST and LDH in serum were detected,and ELISA assay was used to analyze the expression levels of IL-1β,IL-6 and TNF-α in serum;and the apoptotic rate of cardiocytes in each group was measured,and the clearance rate of free radical was determined by absorption spectrometry.Results Compared with control group,the activities of serum CK,AST and LDH in model group were increased obviously(P<0.01);compared with model group,the activities of serum CK,AST and LDH in positive drug and Sal B groups were decreased obviously(P<0.05 or P<0.01).Compared with control group,the levels of serum IL-1β,IL-6 and TNF-α in model group were increased obviously(P<0.01);compared with model group,the levels of serum IL-1β,IL-6 and TNF-α in Sal B group were decreased significantly(P<0.01);but there was no marked change in AsA and BHT groups(P>0.05).Compared with control group,the apoptotic rate of cardiocytes in model group was increased obviously(P<0.01);compared with model group,the apoptotic rate of cardiocytes was decreased significantly in Sal B group(P<0.01);there was no marked change in AsA and BHT groups(P>0.05).Different concentrations of Sal B increased the clearance rate of DPPH free radical with statistical difference(P<0.05).The clearance rates of free radical in Sal B group were higher than those in AsA and BHT groups when the concentrations of Sal B were 20-100 mg·L-1(P<0.05 or P<0.01).Conclusion Sal B has a protective effect on experimental myocardial infarction in rats,and effectively inhibit apoptosis of cardiocytes.Its mechanism may be related to suppression of immune and inflammatory factor secretion and free radical scavenging.