Page 49 - 《中国药房》2024年11期

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
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白 璐 1， 2＊ ，沈士朋 ，吴 苏 ，郭 帅 ，刘茂东 （1.河北医科大学第三医院肾内科，石家庄 050051；2.河
北省糖尿病肾脏疾病重点实验室，石家庄 050051）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2024）11-1327-07
DOI 10.6039/j.issn.1001-0408.2024.11.08

摘 要 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。
关键词 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

Effects of Taohong siwu decoction modified granules on podocyte epithelial-mesenchymal-transition and
renal fibrosis in rats with diabetic kidney disease
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BAI Lu ，SHEN Shipeng ，WU Su ，GUO Shuai ，LIU Maodong （1. Dept. of Nephrology， the Third
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Hospital of Hebei Medical University， Shijiazhuang 050051， China；2. Hebei Provincial Key Laboratory of
Diabetic Kidney Disease， Shijiazhuang 050051， China）
ABSTRACT 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
Δ 基金项目 河北省中医药管理局中医药类科研计划项目（No.
renal tissue were relieved； the thickness of glomerular
2019131，No.2022408）
＊第一作者 副主任中医师，博士。研究方向：肾脏病的中西医结 basement membrane was decreased significantly （P＜0.05）.
合治疗及其机制。E-mail：bailu2011@126.com CONCLUSIONS Taohong siwu decoction modified granules

中国药房 2024年第35卷第11期 China Pharmacy 2024 Vol. 35 No. 11 · 1327 ·