越婢汤调控肾脏毛细血管通透性对阿霉素肾病大鼠水肿的干预作用  

Intervention effects of Yuebi Decoction on edema of rats with adriamycin-induced nephropathy through regulations on renal capillary permeability

作　　者：李婷婷[1,2,3,4] 周圆 徐琳[1,2,3,4] 程苏 邵命海[1,2,3,4] LI Ting-ting;ZHOU Yuan;XU Lin;CHENG Su;SHAO Ming-hai(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Institute of Traditional Chinese Medicine for Kidney Disease,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Ministry of Education Key Laboratory of Liver and Kidney Diseases,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Municipal Key Laboratory for Clinical Practice of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海201203 [2]上海中医药大学中医肾病研究所,上海201203 [3]上海中医药大学肝肾疾病病证教育部重点实验室,上海201203 [4]上海市中医临床重点实验室,上海201203

出　　处：《中成药》2023年第3期748-755,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(81973807);上海市浦东新区卫生系统重点学科群建设资助项目(PWZxq2017-07);上海市进一步加快中医药事业发展三年行动计划(2018年-2020年)资助项目[ZY(2018-2020)-CCCX-2003-08,ZY(2018-2020)-FWTX-7005]。

摘　　要：目的观察越婢汤对阿霉素肾病大鼠肾脏毛细血管通透性的影响,阐明其干预肾病综合征大鼠水肿的作用机制。方法采用尾静脉注射阿霉素建立大鼠肾病综合征模型。大鼠随机分为正常组、模型组及越婢汤低、中、高剂量组(6.6、11.1、22.2 g/kg),灌胃给予相应药物14 d。给药结束后,检测肾脏毛细血管通透性、肾脏及皮肤干湿重比例,观察肾脏病理学变化,检测血清Scr、BUN、TC、ALB及尿液24 h UTP水平,ELISA法检测肾组织VEGF水平,免疫组化法检测肾组织VEGF、VEGFA、VEGFR2阳性表达,Western blot法检测肾组织VEGF、VEGFA、VEGFR2、p-ERK1/2、ERK1/2和Rap1蛋白表达。结果与模型组比较,越婢汤高剂量组大鼠肾脏及皮肤干湿重比例升高(P<0.05,P<0.01),VEGF和VEGFA蛋白表达降低(P<0.01);中、高剂量组大鼠肾脏毛细血管通透性,血清Scr、BUN、TC水平,尿液24 h UTP水平,肾组织VEGF水平和VEGFR2蛋白表达降低(P<0.05,P<0.01),ALB水平升高(P<0.01),肾组织病理学改善;越婢汤各剂量组大鼠肾组织p-ERK1/2/ERK1/2蛋白表达比值降低(P<0.01),Rap1蛋白表达升高(P<0.01)。结论越婢汤可以减轻阿霉素肾病大鼠皮肤和肾脏水肿,其作用机制和调控VEGF/ERK信号通路,改善肾脏毛细血管通透性有关。AIM To clarify the intervention mechanism of Yuebi Decoction on edema in rat models of nephrotic syndrome induced by adriamycin through result ant effects on renal capillary permeability.METHODS Following the establishment of rat models of nephrotic syndrome by adriamycin injection into tail vein,the rats randomly divided into the model group and Yuebi Decoction groups(6.6 g/kg low dose,11.1 g/kg medium dose and 22.2 g/kg high dose)were given 14 days of corresponding intragastric administration,in contrast to the intact rats in the normal group.Subsequently,the rats had their renal vascular permeability and the dry-wet weight ratio of both kidney and skin detected;their renal pathological changes observed;their serum levels of Scr,BUN,TC,ALB and urine 24 h UTP detected;their renal VEGF level detected by ELISA;their renal positive expressions of VEGF,VEGFA and VEGFR2 detected by immunohistochemistry;and their protein expressions of VEGF,VEGFA,VEGFR2,P-ERK1/2,ERK1/2 and Rap1 detected by Western blot.RESULTS Compared with the model group,the high-dose Yuebi Decoction group displayed increased dry-wet weight ratio of kidney and skin(P<0.05,P<0.01),and decreased protein expressions of VEGF and VEGFA(P<0.01).The medium and high dose groups demonstrated decreased renal capillary permeability,serum Scr,BUN,TC levels,24 h UTP level in urine,renal VEGF level and VEGFR2 protein expression(P<0.05,P<0.01),increased ALB level(P<0.01),and improved renal histopathology.All Yuebi Decoction groups shared decreased expression ratio of renal p-ERK1/2/ERK1/2 protein(P<0.01),and increased Rap1 protein expression(P<0.01).CONCLUSION Yuebi Decoction can reduce edema occurring in skin and kidney in rat models of adriamycin nephropathy,and its mechanism may associate with its effects in improving renal capillary permeability through the regulation on VEGF/ERK signaling pathway.

关 键 词：越婢汤 阿霉素肾病 肾病综合征 水肿 毛细血管通透性 VEGF/ERK 

分 类 号：R285.5[医药卫生—中药学]