化瘀方抗大鼠心肌纤维化疗效及其与氧化应激的关系

Effects of Hua-Yu decoction on anti-hypertensive myocardial fibrosis and its relationship with oxidative stress

目的探讨化瘀方对自发性高血压大鼠(SHR)心肌纤维化的疗效及其与氧化应激的关系。方法结合中医理论和网络药理学,预测化瘀方为血府逐瘀汤抗心肌纤维化有效药物组合。SHR分为模型组,化瘀方低、中、高剂量组,血府逐瘀汤组和卡托普利组,Wistar-Kyoto(WKY)大鼠作为正常对照组。超声心动图、无创尾压仪、组织病理学检测心肌纤维化程度,反转录PCR(qRT-PCR)和Western blot检测抗氧化酶的表达。结果与模型组比较,化瘀方低、中、高剂量组射血分数和短轴缩短率增加(P<0.05),血压、肌酸激酶同工酶MB(CK-MB)的表达降低(P<0.05),心肌纤维化减轻,且化瘀方高剂量疗效与血府逐瘀汤组相当。同时,与模型组比较,高剂量化瘀方能增加过氧化氢酶(CAT)、谷胱肽过氧化物酶(GPx)的表达(P<0.05)。结论化瘀方抗大鼠心肌纤维化的疗效可能与减轻氧化应激有关。

Objective To observe the efficacy of Hua-Yu decoction for myocardial fibrosis in spontaneously hypertensive rats(SHR)and its relationship with oxidative stress.Methods Based on the traditional Chinese medicine theory and network pharmacology,we predicted that Hua-Yu decoction was the main effective component of Xue-Fu-Zhu-Yu decoction on anti-hypertensive myocardial fibrosis.12-week-old male spontaneous hypertension rats(SHR)were randomized into six groups:the model group,the Hua-Yu decoction group at low-,medium-,and high-dose,the Xue-Fu-Zhu-Yu decoction group and the captopril group,WistarKyoto(WKY)rats as the model group.The cardiac fibrosis was observed using echocardiography,non-invasive tail pressure gauge and histological examination.The mRNA and protein expression of cellular defense enzymes were determined through quantitative real time poly merase chain reaction(qRT-PCR)and Western blot.Results Compared with the model group,ejection fraction and fraction shortening increased in the HuaYu decoction group at low-,medium-or high-dose(P<0.05),while blood pressure and the expression of creatine kinase-MB(CK-MB)decreased,myocardial fibrosis was inhibited.There was no significant difference between Hua-Yu decoction and Xue-Fu-Zhu-Yu decoction.Moreover,Hua-Yu decoction could increase the expression of catalase(CAT)and glutathione peroxidase(GPX,P<0.05).Conclusion Hua-Yu decoction had the effect of anti-hypertensive myocardial fibrosis,which may be related to alleviating oxidative stress.