调脂通络胶囊对心肌IRI大鼠炎症反应的影响

Influence of Tiaozhi Tongluo Capsules on Inflammatory Response after Myocardial Ischemia Reperfusion Injury

摘要:

目的: 通过测定调脂通络胶囊对心肌缺血再灌注损伤(MIRI)后髓过氧化物酶(MPO)、心梗面积和心肌组织结构形态的变化等,观察调脂通络胶囊对MIRI后的心肌保护作用及可能的机制。 方法: 将大鼠分为调脂通络胶囊高、中、低(8.64,4.32,2.16 g·kg^-1·d^-1)剂量组,高脂模型组、非高脂模型组和阿托伐他汀阳性对照组。喂食高脂饲料4周后药物干预或生理盐水灌胃4周,之后结扎左状动脉前降支30 min后再灌注24 h,采血检测总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和乳酸脱氢酶(LDH)、肌酸激酶(CK-MB),各组一半动物取心肌组织缺血部分测定髓过氧化物酶(MPO),并于靠近心尖部取约0.5 cm²的心肌组织行HE染色,另一半动物伊文思蓝(Evans blue)和氯化三苯基四氮唑(TTC)双染色后,测定心脏缺血和梗死范围质量比率。 结果: 高脂模型组与非高脂模型组相比较梗死范围质量比率、血脂水平和心肌酶含量明显升高(P<0.01)。各药物治疗组与高脂模型组相比可以明显降低MPO和心肌酶含量,减少梗死范围质量比率(P<0.01)。 结论: 调脂通络胶囊和阿托伐他汀可以通过减轻炎性细胞浸润以达到保护心肌细胞的目的,二者的心肌细胞保护作用可能与降低血脂、保护内皮功能有关。调脂通络胶囊无明显剂量依赖性。

Abstract:

Objective:By measuring the level of myeloperoxidase (MPO), infarction weight ratio, myocardial cell morphology, to observe the myocardial protective effects and possible mechanism of Tiaozhi Tongluo capsules for myocardial ischemia-reperfusion injury (MIRI). Method: Ninety-six male Wistar rats were fed with high fat diet for 4 weeks except the non-fat model group. The rats were randomized into six groups and drug intervention or saline for 4 weeks: (1) fat model group; (2) non-fat model group; (3) statin group; (4) Tiaozhi Tongluo capsules 8.64 g·kg^-1·d^-1; (5) Tiaozhi Tongluo capsules 4.32 g·kg^-1·d^-1; (6) Tiaozhi Tongluo capsules 2.16 g·kg^-1·d^-1. The same volume of saline was infused in fat model and non-fat model group. After 2 hours of the last intragastric infusion, the chest was opened and the left anterior desending coronary arteries (LAD) was ligated for 30 min and unclamped for 24 hours for all the rats. After 24 h of reperfusion, the level of blood lipids, cardiac enzymes in serum or the content of MPO in ischemic myocardium tissue (half of the animals of each group) were measured. Myocardial tissue near the apical about 0.5 cm² was taken for HE staining, morphological changes were observed. The myocardial tissue of the rest animals in each group was stained by Evans blue and TTC. Then these slices were immersed in 4% paraformaldehyde formalin, ischemic zone size (IZS), infarct size (IS), the ischemic weight ratio and the infarction weight ratio were determined. Result: The level of cardial enzymes, MPO and infarction weight ratio were significantly higher in fat model group compared to the non-fat model group(P<0.01). The drug treatment groups could significantly reduce the level of cardial enzymes, MPO and infarction weight ratio compared to fat model group(P<0.01). Conclusion: Tiaozhi Tongluo capsules and atorvastatin could protect myocardial cells by reducing the infiltration of inflammatory cells, which might be related to the effects of lowering blood lipids and protecting endothelial function. No clear does-dependent effects were found for Tiaozhi Tongluo capsules.