桃红四物汤加味对糖尿病肾病大鼠肾损伤的影响  

Effect of Modified Taohong Siwu Decoction on Renal Injury in Diabetic Kidney Disease Rats

作　　者：郭倩[1] 王倩[2,3] 郭帅 李敏[2,3] 沈士朋 刘茂东 白璐 GUO Qian;WANG Qian;GUO Shuai;LI Min;SHEN Shipeng;LIU Maodong;BAI Lu(College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University,Shijiazhuang 050017,China;Department of Nephrology,the Third Hospital of Hebei Medical University,Shijiazhuang 050051,China;Hebei Provincial Key Laboratory of Diabetic Kidney Disease,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学中西医结合学院,石家庄050017 [2]河北医科大学第三医院肾内科,石家庄050051 [3]河北省糖尿病肾脏疾病重点实验室,石家庄050051

出　　处：《世界中医药》2025年第1期44-50,60,共8页World Chinese Medicine

基　　金：国家自然科学基金项目(82274504);河北省自然科学基金面上项目(H2021206179);河北省中医药管理局科研计划项目(2019131,2022408)。

摘　　要：目的:基于核因子红系2相关因子2/血红素加氧酶-1(Nrf2/HO-1)信号通路探讨桃红四物汤加味对糖尿病肾病(DKD)大鼠肾损伤的影响。方法:选取8只SD大鼠作为对照组,其余37只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,成模的33只大鼠分为模型组、厄贝沙坦组(13.5 mg/kg)、桃红四物汤加味组(6.48 g/kg)。各组大鼠灌胃给予相应药物和水,共16周。末次给药后检测各组大鼠空腹血糖、血脂、肾功能、24 h尿蛋白定量(24 h UTP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)的变化,观察大鼠肾脏病理变化,检测大鼠肾组织中TNF-α、IL-1βmRNA表达水平,Nrf2、HO-1、NAD(P)H醌氧化还原酶1(NQO1)、转化生长因子β_(1)(TGF-β_(1))、纤连蛋白(FN)mRNA和蛋白的表达水平。结果:与模型组比较,桃红四物汤加味组大鼠血脂、肾功能、24 h UTP显著改善(P<0.05);肾脏病理损伤和纤维化程度减轻;TNF-α、IL-1β含量和mRNA表达水平显著下降(P<0.05);SOD、GSH-Px活性量显著增高(P<0.05),MDA含量显著减少(P<0.05);Nrf2、HO-1、NQO1 mRNA和蛋白的表达水平显著上升(P<0.05),TGF-β_(1)、FN表达水平显著下降(P<0.05)。结论:桃红四物汤加味具有肾保护作用,这可能与其上调Nrf2/HO-1通路相关蛋白表达,减轻炎症反应和氧化应激有关。Objective:To investigate the effect of modified Taohong Siwu Decoction(THSWD)on renal injury in diabetic kidney disease(DKD)rats based on the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods:Eight SD rats were selected as the control group,while 37 other rats were fed a high-glucose,high-fat diet combined with intraperitoneal injection of streptozotocin(35 mg/kg)to establish the DKD model.The 33 successfully modeled rats were divided into the model group,the Irbesartan group(13.5 mg/kg),and the modified THSWD group(6.48 g/kg).Rats in each group were administered the corresponding drugs and water by gavage for 16 weeks.After the final administration,fasting blood glucose,blood lipids,kidney function,24-hour urine protein(24 h UTP),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA)levels were measured.Renal pathological changes were observed,and mRNA expression levels of TNF-αand IL-1β,and mRNA and protein expression levels of Nrf2,HO-1,NAD(P)H quinone oxidoreductase 1(NQO1),transforming growth factor-β_(1)(TGF-β_(1)),and fibronectin(FN)were detected in renal tissue.Results:Compared with the model group,the modified THSWD group showed significant improvement in blood lipids,kidney function,and 24 h UTP(P<0.05).Kidney pathological damage and fibrosis were reduced.The levels of TNF-α,IL-1β,and their mRNA expression significantly decreased(P<0.05),while SOD and GSH-Px activities significantly increased(P<0.05),and MDA levels significantly decreased(P<0.05).The mRNA and protein expression levels of Nrf2,HO-1,and NQO1 were significantly upregulated(P<0.05),while the expression levels of TGF-β_(1) and FN were significantly downregulated(P<0.05).Conclusion:Modified THSWD has a protective effect on the kidneys,which may be related to the upregulation of Nrf2/HO-1 pathway-related protein expression,reduction of inflammation,and oxidative stress.

关 键 词：糖尿病肾病 桃红四物汤加味 肾纤维化 蛋白尿 核因子红系2相关因子2/血红素加氧酶-1信号通路 中医药 炎症反应 氧化应激 

分 类 号：R285.5[医药卫生—中药学]