红花黄色素注射液对急性心肌梗死模型大鼠低氧诱导因子和血管内皮生长因子的影响∗

摘要

目的：探讨红花黄色素注射液对急性心肌梗死大鼠的作用机制。方法 SD大鼠40只,按照随机数字表法分为假手术组8只和手术组32只。手术组采用结扎冠状动脉左前降支复制急性心肌梗死模型,将造模成功大鼠按照随机数字表法分为红花黄色素3 d组、红花黄色素7 d组、红花黄色素14 d组、模型对照组,每组8只。红花黄色素3,7,14 d组分别腹腔注射红花黄色素注射液2.5 mg.kg－1.d－1,分别给药3,7,14 d；假手术组和模型对照组给予等容量0.9％氯化钠溶液。末次给药24 h后称取体质量,处死后测血清乳酸脱氢酶( LDH)和肌酸激酶( CK)含量。采用TTC染色法测量大鼠心脏梗死面积。苏木精-伊红( HE)染色法观察心肌细胞形态的改变。反转录聚合酶链反应( RT-PCR)检测低氧诱导因子(HIF)、血管内皮生长因子(VEGF)mRNA的表达。结果假手术组LDH和CK分别为(106.12±35.52),(452.84±60.38)mmol.L－1,模型对照组分别为(385.66±137.58),(2111.00±1250.80)mmol.L－1。红花黄色素3,7,14 d组LDH分别为(249.66±51.86),(104.33±51.08),(110.33±26.76)mmol.L－1,其中红花黄色素14 d组明显小于模型对照组(P<0.05)；CK分别为(1713.00±584.74),(1177.66±980.18),(421.33±54.60)mmol.L－1,其中红花黄色素14 d组明显小于模型对照组(P<0.05)；假手术组梗死面积(0.00±0.00)％,模型对照组为(13.12±6.69)％,红花黄色素3,7,14 d组分别为(8.11±3.45)％,(7.01±2.98)％,(3.44±1.17)％,红花黄色素14 d组心肌梗死面积明显小于模型对照组(P<0.05)。假手术组HIF和VEGF mRNA表达分别为1.99±0.27,6.21±1.35,模型对照组分别为1.03±0.15,1.78±0.57,红花黄色素3,7,14 d组HIF mRNA分别为0.50±0.12,1.23±0.24,2.20±0.32；VEGF mRNA分别为0.43±1.27,2.67±0.83,5.78±1.23,其中红花黄色素14 d组HIF mRNA和VEGF mRNA明显小于模型对照组( P<0.05)。结论红花黄色素注射液治疗14 d可减小急性心肌梗死大鼠的梗死面积,降低心肌酶,其作用机制可能与上调HIF和VEGF mRNA表达有关。%Objective To probe into impacts of safflor yellow injection on rats with acute myocardial infarction and discuss its mechanism. Methods Forty Sprague-Dawley rats were divided into sham operation group ( 8 rats ) and operation groups(32 rats).The left anterior descending branch of coronary artery was ligated to establish an animal model with acute myocardial infarction.The rats with successful modeling were randomly divided into model control group, 3-, 7- and 14-days safflor yellow group.In the treatment group, the rats were injected with safflor yellow injection(2.5 mg.kg-1.d-1)for 3, 7 and 14 days, respectively.Rats in sham operation and model control group were injected 0.9% sodium chloride solution.Their weights were measured 24 h after the last drug administration, their hearts were removed, and the serum was obtained through centrifugation.The enzymic method was used to measure the lactate dehydrogenase(LDH)and creatine kinase(CK)contents of serum.Hematoxylin eosiny(HE)staining method was used to observe the change of myocardial cells.The chloride three phenyl-tetrazole( TTC) staining method was used to measure the area of myocardial infarction in the rats. The real-time fluorescent quantitative PCR method was used to measure the expression of VEGF and HIF mRNA at the marginal zone of myocardial infarction. Results The levels of LDH and CK were(106.12±35.52),(452.84±60.38)mmol.L-1 in sham operation group, and(385.66±137.58),(2 111.00±1 250.80)mmol.L-1 in model control group.LDH in 3-, 7-, 14-days treatment groups was (249.66±51.86),(104.33±51.08),(110.33±26.76)mmol.L-1, while CK was(1 713.00±584.74),(1 177.66±980.18), (421.33±54.60)mmol.L-1.LDH and CK levels of the 14-days treatment group were significantly lower than those in the model control group(both P<0.05).The area of myocardial infarction was (0.00±0.00)% in sham operation group,(13.12±6.69)% in the model control group, and(8.11±3.45)%,(7.01±2.98)%,(3.44±1.17)% in the 3-, 7-, 14-days treatment groups.The area of myocardial infarction in the 14-days treatment group was significantly lower than that of the model control group(P<0.05).The expression of VEGF and HIF mRNA was 1.99±0.27, 6.21±1.35 in the sham operation group, 1.03±0.15, 1.78±0.57 in the model control group.The expression of HIF mRNA in the 3-, 7-, 14-days treatment groups was 0.50±0.12, 1.23±0.24, 2.20± 0.32, and the expression of VEGF mRNA in the 3-, 7-, 14-days treatment groups was 0.43±1.27, 2.67±0.83, 5.78±1.23. Conclusion The safflor yellow injection has therapeutical effects on the rats with acute myocardial infarction, and the effects will become significant after 14 day.It can reduce the area of myocardial infarction and LDH and CK content at the drug administration groups, which might be related to the increase of the expression of VEGF and HIF mRNA.