清肝益肾祛风复方抗高血压肾损伤作用及机制研究  

The Effects and Mechanisms of Qingganyishenqufeng Formula on Hypertensive Renal Injury

作　　者：吴丹丹[1,2] 陈瑜[1,2] 张腾[1,2] WU Dandan;CHEN Yu;ZHANG Teng(Yueyang Integrated Traditonal Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,200001)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200001 [2]上海市中医药研究院中西医结合临床研究所,上海200001

出　　处：《中国中西医结合肾病杂志》2019年第6期478-482,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：上海市东方学者跟踪计划项目(No.GZ2015011、沪教委人[2017]64号);上海市进一步加快中医药事业发展三年行动计划项目(2018年~2020年)(No.ZY[2018-2020]-CCCX-2004-07);国家中医药管理局中西医结合临床重点学科建设项目(No.国中医药发〔2009〕30号);上海市优秀学术带头人(No.14XD1403500)

摘　　要：目的:探究清肝益肾祛风方对自发性高血压大鼠的降压、抗高血压肾损伤作用及其可能的作用机制,以期为临床治疗高血压肾损伤提供科学依据。方法:采用4周龄雄性SHR大鼠作为高血压模式动物,适应性饲养一周后随机分为SHR模型组、坎地沙坦治疗组,清肝益肾祛风方(QYQ)治疗组。正常对照组选用同周龄雄性WKY大鼠。从6周龄开始,QYQ治疗组和坎地沙坦治疗组每天分别给予2 ml的清肝益肾祛风方水煎液和坎地沙坦悬液灌胃。SHR组和WKY组采用同等体积的纯水做为对照,连续灌胃至20周龄。采用小动物无创血压计每2周测量一次血压;连续给药至20周龄后,10%水合氯醛腹1腔注射麻醉、腹主动脉取血后处死动物。留取双侧肾脏、采用离心机分离血清。左肾脱水固定包埋后做石蜡切片,Masson’s trichrome染色观察左侧肾脏组织病理变化;采用全自动生化检测仪检测大鼠血清中尿素、肌酐、尿酸水平;Realtime PCR方法检测右侧肾脏组织氧化应激标志物相关基因的mRNA表达水平、炎症因子基因的mRNA表达水平及胶原相关基因的mRNA表达水平。结果:与WKY组相比,SHR组大鼠血压从6周龄开始显著升高(P<0.05),从12周龄开始达到稳定;与SHR组相比较,清肝益肾祛风方与坎地沙坦均能显著降低SHR大鼠血压(P<0.05);Masson’s trichrome染色结果:WKY组肾脏组织未见病理损伤,SHR组大鼠肾脏组织出现较大面积纤维化。与SHR组相比,QYQ治疗组与坎地沙坦治疗组肾脏组织纤维化面积均显著降低(P<0.05);生化检测结果提示:与WKY组相比,SHR组血清中尿酸、尿素含量显著升高(P<0.05)。与SHR相比较,QYQ治疗组血清尿酸含量显著降低(P<0.05)。Real-time PCR结果:与WKY组相比,SHR组肾脏组织氧化应激相关基因mRNA表达水平显著升高(P<0.05),IL-23,TNF-α及TGF-β1等炎症因子相关基因的mRNA表达水平显著升高(P<0.05),IL-10基因的mRNA表达水平显著降低Objective: To provide scientific basis for the clinical application of Qinggan Yishen Qufeng formula(QYQ) in the treatment of hypertensive renal injury,the effects and mechanisms of QYQ on hypertension and hypertensive renal injury were investigated in spontaneously hypertensive rats(SHR).Methods: Six-week-old male SHR rats were randomly designated as SHR model group,candesartan-treatment group and QYQ-treatment group were daily gavaged with 2 ml of vehicle,Candesartan suspension and QYQ,respectively. Age-matched male WKY rats served as normal controls and received vehicle treatment in the same manner. The indicated treatment were administered for 14 weeks. Blood pressure was measured every 2 weeks using the noninvasive sphygmomanometer for small animals. The renal fibrosis was assessed by Masson’s trichrome staining,The serum concentrations of urea,creatinine and uric acid were detected by a biochemical detector. Real-time PCR was used to analyze the mRNA expression levels of oxidative stress-related genes,proinflammatory genes,and fibrosis-related genes in the kidney.Results: Compared to that from the vehicle-treated WKY normal controls,the blood pressure of the vehicle-treated SHR was significantly increased(P< 0.05). Compared to that from the vehicle-treated SHR group,QYQ and Candesartan treatment result in significantly reduced blood pressure in SHRs(P<0.05). Compared to normal renal histology in the vehicle-treated WKY controls,over renal fibrosis was observed the vehicle-treated SHRs. Compared to that from the vehicle-treated SHRs,the renal fibrotic area was significantly decreased in QYQ-treated SHRs and candesartan-treated SHRs(P<0.05). The biochemical test results showed that the serum levels of uric acid and urea were significantly higher in the vehicle-treated SHRs compared to that from the vehicle-treated WKY controls(P<0.05). Compared to that from the vehicle-treated SHRs,the serum levels of uric acid was significantly decreased in QYQ treatment SHRs(P<0.05). Real-time PCR results revealed that co

关 键 词：清肝益肾祛风 高血压肾损伤 氧化应激 炎症 纤维化 

分 类 号：R285.5[医药卫生—中药学]