桃红四物汤加味颗粒对糖尿病肾病模型大鼠足细胞上皮-间充质转化及肾脏纤维化的影响OA北大核心CSTPCD
Effects of Taohong siwu decoction modified granules on podocyte epithelial-mesenchymal-transition and renal fibrosis in rats with diabetic kidney disease
目的 探讨桃红四物汤加味颗粒对糖尿病肾病(DKD)模型大鼠足细胞上皮-间充质转化(EMT)及肾脏纤维化的影响.方法 随机选取8只大鼠为正常组(予普通饲料),其余大鼠采用高糖高脂饲料联合腹腔注射链脲佐菌素(35 mg/kg)建立DKD模型.将模型大鼠分为模型组、厄贝沙坦组[阳性对照,13.5 mg/(kg·d)]、桃红四物汤加味组[6.48 g/(kg·d)],每组最终纳入8只.各组大鼠灌胃相应药物,每日1次,连续干预16周.干预第4、8、12、16周末检测各组大鼠24 h尿蛋白(24 h UTP),末次给药后检测各组大鼠体重、饮水量、饮食量、尿量、空腹血糖、血肌酐(Scr)、尿素氮(BUN)和肾组织中P-钙黏素(P-cadherin)、足细胞裂孔膜蛋白(nephrin)、α-平滑肌肌动蛋白(α-SMA)、肾母细胞瘤蛋白1(WT1)、转化生长因子β1(TGF-β1)、Ⅳ型胶原蛋白(Col-Ⅳ)mRNA及蛋白的表达情况,观察肾组织病理形态学变化并测量肾小球基底膜厚度.结果 与模型组比较,桃红四物汤加味组大鼠从第8周末开始24 h UTP显著降低,体重显著增长,饮水量、尿量均显著减少,Scr、BUN水平和α-SMA mRNA以及TGF-β1、Col-Ⅳ mRNA及蛋白表达水平均显著降低,P-cadherin、nephrin、WT1 mRNA表达水平均显著升高(P＜0.05);α-SMA蛋白沉积减少,P-cadherin、nephrin、WT1蛋白沉积均增多;大鼠肾组织病理损伤及纤维化程度减轻,肾小球基底膜厚度显著减小(P＜0.05).结论 桃红四物汤加味颗粒可通过抑制DKD模型大鼠足细胞EMT,减轻肾组织病理损伤及足细胞损伤,从而保护肾功能、延缓肾脏纤维化进展.
OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial-mesenchymal-transition(EMT)and renal fibrosis in diabetic kidney disease(DKD)model rats.METHODS Eight rats were selected as normal group(ordinary feed);the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin(35 mg/kg)to induce the DKD model.Model rats were randomly divided into model group,irbesartan group[positive control,13.5 mg/(kg·d)]and modified Taohong siwu decoction group[6.48 g/(kg·d)],with 8 rats in each group.All groups were given relevant medicine intragastrically,once a day,for 16 consecutive weeks.Twenty-four-hour urinary total protein(24 h UTP)was detected at the end of the 4th,8th,12th and 16th week of administration.After the last medication,the body mass,water intake,food intake,urine output,the levels of fasting blood glucose,serum creatinine(Scr)and blood urea nitrogen(BUN)as well as mRNA and protein expressions of P-cadherin,nephrin,α-smooth muscle actin(α-SMA),Wilms'tumor gene 1(WT1),transforming growth factor-β1(TGF-β1)and type Ⅳ collagen(Col-Ⅳ)in renal tissue were determined.The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined.RESULTS Compared with the model group,24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend(P＜0.05);the body weight of rats increased significantly,but the amount of water intake and urine decreased significantly;Scr and BUN level,mRNA expression of α-SMA,mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced,while the mRNA expressions of P-cadherin,nephrin and WT1 were increased significantly(P＜0.05);the protein deposition of α-SMA was reduced,protein depositions of P-cadherin,nephrin and WT1 were increased;the pathological damage and fibrosis of renal tissue were relieved;the thickness of glomerular basement membrane was decreased significantly(P＜0.05).CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats,and alleviate renal pathological damage and podocyte damage,thus protecting renal function,and delaying the process of renal fibrosis.
白璐;沈士朋;吴苏;郭帅;刘茂东
河北医科大学第三医院肾内科,石家庄 050051||河北省糖尿病肾脏疾病重点实验室,石家庄 050051
药学
糖尿病肾病桃红四物汤加味颗粒肾脏纤维化足细胞上皮-间充质转化
diabetic kidney diseaseTaohong siwu decoction modified granulesrenal fibrosispodocyteepithelial-mesenchymal-transition
《中国药房》 2024 (011)
1327-1333 / 7
河北省中医药管理局中医药类科研计划项目(No.2019131,No.2022408)
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