[关键词]
[摘要]
目的 探讨真武汤对慢性心力衰竭(CHF)大鼠的治疗作用,并分析其潜在作用机制。方法 建立真武汤的HPLC特征图谱;雄性SD大鼠随机分为假手术组、模型组、阳性药卡托普利组(10 mg/kg)和真武汤低、中、高剂量(2.187 5、4.375、8.75 g/kg)组,除假手术组外,其余大鼠均通过结扎冠状动脉左前降支复制CHF大鼠模型,8周后ig给药,共给药4周。实验末进行血流动力学、脏器指数、HE染色检测,ELISA试剂盒测定大鼠血清血管紧张素II(Ang II)、醛固酮(ALD)、核转录因子-κB(NF-κB)、氨基末端脑钠肽(NT-proBNP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,Western boltting检测心肌NF-κB蛋白表达情况。结果 真武汤HPLC图谱中指认出5个化学成分去甲乌药碱、芍药苷、白术内酯III、6-姜辣素、去氢土莫酸;与模型组比较,真武汤给药后能改善大鼠血流动力学相关参数(P<0.05),降低脏器指数(P<0.05),改善心肌损伤,降低血清Ang II、ALD、NF-κB、NT-proBNP、TNF-α、IL-6水平及心肌NF-κB蛋白表达水平(P<0.05)。结论 真武汤能够改善CHF,其机制可能与抑制肾素-血管紧张素-醛固酮系统(RAAS)/NF-κB/炎症因子级联反应有关。
[Key word]
[Abstract]
Objective To investigate the therapeutic effect and potential mechanism of Zhenwu Decoction (ZWD) on chronic heart failure (CHF) rats. Methods HPLC fingerprint of ZWD was established. All male SD rats were randomly divided into the sham operation group, the model group, the low, medium and high dose ZWD group (2.187 5, 4.375, and 8.75 g/kg) and the captopril group (10 mg/kg). Except for the sham operation group, the rest of rats were all established into the CHF model rats by ligating the left anterior descending branch of the coronary artery, after 8 weeks, all rats were ig administration for 4 weeks. The hemodynamic, viscera index, HE dyeing test were conducted at the end of experiments. Serum angiotensin II (Ang II), aldosterone (ALD), nuclear factor kappa B (NF-κB), amino terminal brain natriuretic peptide (NT-proBNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) were determinated by ELISA, and myocardial NF-κB protein expression was detected by Western blotting. Results Higenamine, paeoniflorin, atractylenolide III, 6-gingerol and dehydrotumulosic acid, the five constituents of Zhenwu Decoction, were identified by HPLC chart. Compared with the model group, the administration of the ZWD significantly improved the hemodynamic parameters (P<0.05), reduced the organ index (P<0.05) and improved myocardial injury, reduced the serum Ang II, ALD, NF-κB, NT-proBNP, TNF-α and IL-6 levels and the myocardial NF-κB protein expression (P<0.05). Conclusion HPLC results provided an evidence for the quality control and pharmacodynamic substance of ZWD. ZWD can ameliorate CHF, which may be related to the inhibition of renin-angiotensin-aldosterone system (RAAS)/NF-κB/inflammatory factor cascade reaction.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(81773988);国家重点研发计划项目(2017YFC1701600);安徽省科技重大专项(18030801131);安徽省地方科技创新项目示范(201907d07050002);全国大学生创新创业训练计划项目(2017043)