当归芍药散对肾病综合征大鼠水肿的改善作用及机制  

Study on improvement effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and its mechanism

作　　者：马晓雯 范胜楠 许在平 项庆镇 宣自华 王运来 许钒 MA Xiao-wen;FAN Sheng-nan;XU Zai-ping;XIANG Qing-zhen;XUAN Zi-hua;WANG Yun-lai;XU Fan(School of Pharmacy,Anhui University of Chinese Medicine,Anhui Province Key Laboratory of Chinese Medicinal Formula,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,中药复方安徽省重点实验室,安徽合肥230012

出　　处：《中国药理学通报》2024年第6期1172-1178,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81974536,82274375);安徽省科技重大专项资助项目(No 202203a07020006)。

摘　　要：目的探究当归芍药散对肾病综合征大鼠水肿的改善作用及作用机制。方法将大鼠随机分为正常组、模型组、当归芍药散组(17.2 g·kg^(-1)·d^(-1))、氯沙坦组(30 mg·kg^(-1)·d^(-1))、托伐普坦组(3 mg·kg^(-1)·d^(-1))。尾静脉注射阿霉素建立肾病综合征大鼠模型。给药4周后,检测各组大鼠肾功能指标及24 h尿蛋白含量变化;免疫组化法检测肾组织中水通道蛋白2(aquaporin 2,AQP2)和pS256-AQP2的分布;放射免疫法测定血浆精氨酸加压素(arginine vasopressin,AVP)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平;Western blot和RT-PCR法分别检测肾脏AQP2、pS256-AQP2、血管紧张素1型受体(angiotensin type 1 receptor,AT1R)、精氨酸加压素受体2(arginine vasopressin receptor 2,V2R)蛋白及mRNA的表达。结果3种药物均可改善肾病综合征大鼠肾功能,减轻蛋白尿,降低血浆AVP及AngⅡ水平,下调AQP2、pS256-AQP2蛋白和mRNA表达。当归芍药散与托伐普坦对于降低血浆AVP水平的效果优于氯沙坦。结论当归芍药散可能通过降低AVP及AngⅡ水平,进而调节AQP2的表达,改善肾病综合征大鼠水肿。Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg^(-1)·d^(-1)),losartan group(30 mg·kg^(-1)·d^(-1))and tolvaptan group(3 mg·kg^(-1)·d^(-1)).The rat model of nephrotic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohistochemistry.The levels of plasma arginine vasopressin(AVP)and angiotensinⅡ(AngⅡ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang II levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more effective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and AngⅡ,and improve the edema of nephrotic syndrome rats.

关 键 词：肾病综合征 水肿 水通道蛋白2 精氨酸加压素 血管紧张素Ⅱ 当归芍药散 

分 类 号：R-332[医药卫生] R289.5R322.61R442.5R692