苦瓜总皂苷对慢性心衰大鼠Caspase-3和MMP-2表达影响

Effects of Momordica Charantia Saponins on the Expression of Caspase-3 and MMP-2 in Rats with Chronic Heart Failure

目的：探讨分析苦瓜总皂苷对慢性心衰大鼠心脏组织中Caspase-3和MMP-2表达的影响。方法：60只SD大鼠按照随机数字法分为正常组、模型组以及苦瓜总皂苷低、中和高剂量治疗组,每组12只,适应性喂养14d后给予注射盐酸去甲肾上腺素（ISO）构建心衰大鼠模型,模型建立成功后,苦瓜总皂苷低、中和高剂量组分别给予苦瓜总皂苷10、20和40 mg/（kg·d）皮下注射,注射时分散于500μL的生理盐水中,正常组和模型组则给予等量的生理盐水注射,8周后采用超声仪评价大鼠心功能指标,同时检测炎性因子TNF-α和IL-10含量,免疫组化、Western以及实时荧光定量PCR检测心肌组织中Caspase-3和MMP-2表达的特点。结果：在实验期内,模型组大鼠有明显精神萎靡,同时饮食量均降低,苦瓜总皂苷3个治疗组可明显改善上述症状,此外模型组有3只死亡,苦瓜总皂苷低、中和高剂量组分别死亡2只、2只和1只;与正常组相比,模型组LVDD和LVDS明显升高（P〈0.05）,LVEF和LVFS明显降低（P〈0.05）,与模型组相比,苦瓜总皂苷低剂量和中剂量组没有明显改善,而苦瓜总皂苷高剂量组LVDD和LVDS明显降低（P〈0.05）,LVEF和LVFS则明显升高（P〈0.05）;此外苦瓜总皂苷3个治疗组可以明显降低炎性因子TNF-α和IL-10的表达;与正常组相比,模型组Caspase-3和MMP-2表达明显升高（P〈0.05）,与模型组相比,苦瓜总皂苷3个治疗组则可以明显降低其表达（P〈0.05）。结论：苦瓜总皂苷能够有效改善ISO所致的慢性心衰大鼠心功能,降低炎症反应,其机理可能与其可以抑制心脏组织中Caspase-3和MMP-2的表达有关。

Objective：To investigate the effect of Momordica charantia saponins on the expression of Caspase-3 and MMP-2 in the heart of rats with chronic heart failure. Methods：Sixty SD rats were randomly divided into the normal group,model group and Momordica charantia saponins group. After successful builting the model,Momordica charantia saponins was given 10,20 and 40 mg/（kg·d）to the low,medium and high dose groups（before injection,Momordica charantia saponins were dispersed in 500 μL）,and the control and model groups were given normal saline respectively. After 8 weeks,the rats were sacrificed after ultrasonic detected. The levels of TNF-α and IL-10 were detected. Immunohistochemistry,Western and real-time quantitative PCR were used to detected the expression of Caspase-3 and MMP-2 in myocardium. Results：During the experimental period,the rats were significantly lethargic,and the dietary intake was decreased in the model group,three doses of Momordica charantia saponins groups could improve for the above symptoms. In addition,there were 3 rats were died in the model group（P〈0.05）,compared with the normal group,LVEF and LVFS were significantly decreased（P〈0.05）and the LVDD and LVDS were significantly higher in the model group（P〈0.05）,after using the Momordica charantia saponins treated,the LVEF and LVFS were significantly increased and the LVDD and LVDS were significantly decreased in Momordica charantiasaponins high does group（P〈0.05）,there was no statistical significance in the low dose and middle dose group compared with the model group（P〈0.05）The expression of Caspase-3 and MMP-2 in the heart tissue was detected by immunohistochemistry,Western blot and real-time quantitative PCR. And the results found the expression of Caspase-3 and MMP-2 of the heart tissue in the model group were significantly higher than them in the normal group（P〈0.05）. Compared with the model group,the expression of Caspase-3 and MMP-2 were significantly higher than them in the model group（P〈0.05）. Conclusion：Momordica charantia saponins could effectively improve the cardiac function and decrease the inflammatory response in rats with chronic heart failure. The mechanism may be related with this new drug can inhibit of the Caspase-3 and MMP-2 expression in cardiac tissue.