血府逐瘀胶囊对高脂合并心梗大鼠心肾功能的影响及作用机制探讨

【作者】 李腾飞；

【导师】 杜金行；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2012， 硕士

【摘要】 背景近年来,心肾综合征备受临床关注,其定义为“心脏和肾脏中某一个脏器的急性或慢性功能不全导致另一个脏器出现急性或慢性功能障碍的临床综合征”。心肾综合征病理机制复杂,是临床常见的疑难重症。依照不同发病特点,将其分为五型,但各型临床流行病学资料及治疗手段依然有限。心肾综合征的病理机制主要有血流动力学改变、炎症反应、RAAS过度激活、交感神经系统激活、NO-ROS失衡、贫血与铁缺乏等方面,上述各种机制相互影响,互相促进,最终形成恶性循环。本课题将初步观察炎症反应在心肾综合征中的作用。研究表明,血清总胆固醇或低密度脂蛋白胆固醇升高是心脑血管疾病的独立危险因素之一。为此,对血脂异常的防治必须及早给予重视,但我国目前血脂控制达标率不足30%,高脂血症的防治工作任重而道远。众多研究发现,以血府逐瘀汤为代表的活血化瘀治则治疗心、肾疾病疗效显著,并能有效的降低血脂水平,显示出良好前景。目的通过本研究,以期明确大鼠心梗后心肾功能变化及炎症因子表达情况,本研究主要观察ICAM-1和IL一6。并探索活血化瘀治则对模型动物肾脏损害的干预情况及作用环节,为缺血性心脏病肾损害的基础研究及防治对策提供方法和思路。方法参照文献方法,采用结扎大鼠左冠状动脉前降支的方法制备大鼠心肌缺血模型,动物分为正常对照组、正常对照假手术组、高脂对照组、高脂假手术组、高脂模型组、血府逐瘀汤5倍组、血府逐瘀汤10倍组,每组动物8只,术后饲养14天后取材,检测心电图、血尿生化、血清中炎性因子、肾组织形态学变化以及肾脏代谢组学变化。结果1、活血化瘀药物治疗后模型动物缺血心电图阳性率降低；2、高脂大鼠心肌梗死后血肌酐明显升高(P<0.05),内生肌酐清除率明显下降(P<0.05)；3、高脂大鼠心肌梗死后血清ICAM-1、IL-6含量明显升高(P<0.01)；4、活血化瘀药物治疗后模型动物血肌酐有下降趋势、内生肌酐清除率提高,但未见统计学差异(P>0.05)。血清炎症因子ICAM-1、IL-6的含量较模型组略有降低,但未见统计学差异(P>0.05)。结论高脂大鼠心肌梗死后会出现肾脏损害,并可见循环中炎症因子表达升高,血府逐瘀对肾功能有一定改善作用。血府逐瘀胶囊治疗可以降低大鼠血清胆固醇及低密度脂蛋白含量。更多还原

【Abstract】 BackgroundCardiorenal syndrome receives much concern in recent years. The latest definition of CRS was "a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of1organ may induce acute or chronic dysfunction of the other". The pathologic mechanism of CRS is very complicated. It’s a difficult and complicated diseases in clinical work. According to the different pathogenesis characteristics, the CRS was divided into five types. The data of clinical epidemiologic investigation and therapy methods is still limited. The main pathologic mechanism of CRS were hemodynamic changes, inflammatory response, over-activation of RAAS, activation of sympathetic nervous, NO-ROS imbalance, anemia and iron deficiency and so on. They interacte and promote each other. A vicious circle will formate in final. The current project will make a deep research on the role of inflammatory response in cardiorenal syndrome. The results show that elevated serum total cholesterol or LDL cholesterol is an independent risk factor for coronary heart disease and ischemic stroke. So, we must give attention to early prevention and treatment of dyslipidemia. But China’s current lipid control compliance rate is still less than30%. There is a long way to prevent and control hyperlipidemia. Many studies have found that promoting blood circulation therapy(Xuefuzhuyutang as the representative) can get significant effect in treatment of heart and kidney disease, and it can effectively reduce blood lipid levels.ObjectiveIn this study, the main object is to clear the change of heart anf kidney function, and the inflammatory factors expression in kidney injury. The main indicator are ICAM-1and NF-κB. To explore the intervention effect of promoting blood circulation therapy. Provide methods and clues for basic research and prevention countermeasures in CRS.MethodsAccording to the methods in literaries, we lagated the LAD to make the mode of myocardial ischemia. Animals was divited into normal control group, normal control sham operation group, high-fat control group, Fat sham surgery group, Model group, Xuefuzhuyu five times group, Xuefuzhuyu ten times group,8rats in each group. Before drawing materials, all the rats received feeding for14days. And then, we check the ECG, blood and urine biochemistry, Inflammatory Factors in Blood serum, the nephrotic management histological changes and metabolomics changes of the kidney.Results1.The positive rate of ischemic ECG decreased after the therapy of promoting blood circulation and removing blood stasis;2.The serum creatinine increased and creatinine clearance rate (Ccr) declined after MI in hyperlipidemia rats(P<0.05);3.The serum level of ICAM-1,IL-6increased after the MI(P<0.01);4. After the therapy of promoting blood circulation and removing blood stasis, we can observe the downward trend of serum creatinine and the upward trend of Ccr, but no significant difference(P>0.05). At the same time, the serum level of ICAM-1,IL-6slightly lower than model group, but no significant difference(P>0.05). ConclusionKidney injuey could be observed after myocardial ischemia in hyperlipidemia rats, and the expression of inflammatory factors was increased. Promoting blood circulation therapy could reduce the degree of renal impairment caused by myocardial ischemia and reduce the level of TC and LDL-C.更多还原