降压通脉方对自发性高血压大鼠肾脏损害的实验及机理研究

【作者】 曹征；

【导师】 金章安；

【作者基本信息】 北京中医药大学 ， 中西医结合内科学， 2007， 硕士

【摘要】 高血压肾损害是指高血压病导致的小动脉性肾脏硬化，以良性肾血管硬化为主。现代医学研究高血压病至少可以通过两条作用途径：即高血压促进动脉粥样硬化形成所致的肾组织缺血性病变，以及通过肾小球高压力和高灌注造成的肾组织的损伤导致高血压病肾损害。此外，肾组织中细胞外基质的聚集及细胞因子均参与高血压所致肾动脉、肾小球及小管间质的病变过程。有研究表明，高血压病对心脏、肾脏同时产生损害，损害程度具相关性。现代医学常规治疗措施虽然能改善血流动力学，缓解部分症状，但不能影响高血压肾损害的进程，并且ACEI和ARB类药物在肾功能损害达到一定程度（血清肌酐[Scr]> 3mg/dl）时，其应用受到限制，因此中医药治疗高血压肾损害成为值得探讨的途径。本研究中，通过降压通脉方对自发性高血压大鼠（SHR）进行早期干预，观察中药复方对肾早期损害指标(二十四小时尿微量白蛋白的排泄、尿NAG酶)的表达及其与肾损害的关系的影响，为中药防治高血压肾损害提供客观依据。方法：以同龄雄性正常血压大鼠（WistarKyoto, WKY）和自发性高血压大鼠（SHR）为研究对象，在14周龄时，随机分为正常组（给予生理盐水）、中药组（给予降压通脉方）、西药组（给予卡托普利），空白对照组（给予生理盐水），每隔两周测量SHR大鼠尾动脉血压（arteria caudilis pressure），给药14周后，即大鼠28周龄时，取大鼠24h尿液检测尿微量白蛋白及尿NAG酶。结果：同正常组（WKY）组相比，自发性高血压大鼠（SHR）各组血压及24小时尿微量白蛋白和尿NAG酶显著增高（P〈0.01〉，鼠尾动脉收缩压显著增高。和空白对照组比较中药组，西药组鼠尾动脉血压均显著降低（P〈0.01）；西药组降压作用更显著并与中药组比较具有差异性（P〈0.05），与空白对照组比较中药组和西药组可以显著降低24h尿β2-MG及尿NAG酶（P〈0.05），中药组降低作用更显著并与西药组比较具有差异性（P〈0.05），从实验结果上看肾脏保护作用中药组优于西药组。结论：中药降压通脉方对自发性高血压大鼠的血压控制有效，但降压通脉方降压效果逊于西药开博通；降压通脉方对高血压病肾损害的肾脏的保护作用要优于卡托普利（开博通）。更多还原

【Abstract】 Hypertension nephrosclerosis (HN) refers to arteriolarnephrosclerosis caused by high blood pressure, the most of which isbenign nephridial angiosclerosis. At least, there are two methods to studyhigh blood pressure in modern medicine: one is that the atherosis lead byhypertension causes the anoxic pathological changes in nephridial tissue;the other is that HN begotten by a kidney hurt via glomerulus highpressure and high precessurese. Besides, the condensation of excellularmatrix and some special cytokines in nephridial tissue can cause thepathological changes of renal artery, renal glomerulus, and nephric tubulematrix lead by hypertension. Some studies show that high blood pressuredo harm to heart and kidney simultaneously and relatively. The routinetherapy of modern medicine can improve the indications of blood flowdynamics and ameliorate symptom partially, but it can not change theprogress of HN. Furthermore, when kidney function is harmed to someextent (Scr>3mg/dl), the application of ACEI and ARB is limited;therefore, the therapies of traditional chinese medicine (TCM) to HN arevaluable to attempt.In this report, we applied normal male wistar Kyoto (WKY) rat andspontaneously hypertensive rat (SHR) and planed to treat them with JiangYa Tong Mai Fang at the early stage, and observe the influence of theTCM therapy to the expression of indications (blood,β2-MG,24h urinealbumin, NAG, Scr and UN) of earlier phase ranodamage and therelationship of the indications and earlier phase ranodamage, in order toprovide grounds for preventing and curing HN with TCM. The WKY ratsand SHR rats in the experiments were 14 weeks old, and the rats weredivided into normal group (treated with physiological saline), TCM group(treated with Jiang Ya Tong Mai Fang), western medicine group (WM,treated with Captopril), and control group (treated with physiologicalsaline) according to theβ2-MG in 24h urine albumin and NAG. TheSHR rats were measured arteria caudilis pressure every two weeks. Whenall the experiment groups were treated for 14 weeks, i.e., the rats were 24weeks old, theβ2-MG in 24h urine albumin and NAG of the rats weresampled and examined. Compared to the WKY rats, blood pressure,β2-MG in 24h urine albumin (P<0.01) of SHR rats in each group raisedremarkably, and the arteria caudilis pressure of SHR rats raised obviously,too. When compared with TCM group , WM group and control to groups,we found that the situation of blood pressure of WM group is better thanthat of TCM group, but theβ2-MG in 24h urine albumin and NAG ofTCM group is better than that of WM group and control group. Theresults of the experiments exhibited that the difference of arteria caudilispressure between SHR rats and WKY rats in each group is not significant. The arteria caudilis pressure of TCM group is significantly lower than thatof control group, but higher than that of WM group; theβ2-MG in 24hurine albumin and NAG of TCM group is significantly lower than that ofWM group and control group. Based all the data in the experiments, wecan draw the following conclusions: high blood pressure does great harmto kidney. Compound Jiang Ya Tong Mai Fang can regulate the bloodpressure of SHR rats, but the curing effect of which is not better than thatof Captopril. The protective effects on kidney damaged by HN ofcompound Jiang Ya Tong Mai Fang is prior to the single western medicine.更多还原