基于转化生长因子β_(1)/哺乳动物雷帕霉素靶蛋白探讨黄芩苷对糖尿病模型大鼠的肾功能保护作用及机制  

Protective Effect and Mechanism of Baicalin on Renal Function in Diabetes Mellitus Model Rats Based on TGF-β_(1)/mTOR

作　　者：李进冬[1,2] 高一 李智勤 花慧莲[1] LI Jindong;GAO Yi;LI Zhiqin;HUA Huilian(Taizhou People′s Hospital,Taizhou,Jiangsu,China 225300;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou,Jiangsu,China 221004;Kangda College of Nanjing Medical University,Lianyungang,Jiangsu,China 222000)

机构地区：[1]江苏省泰州市人民医院,江苏泰州225300 [2]江苏省新药研究与临床药学重点实验室,江苏徐州221004 [3]南京医科大学康达学院,江苏连云港222000

出　　处：《中国药业》2023年第13期46-50,共5页China Pharmaceuticals

基　　金：江苏省新药研究与临床药学重点实验开放课题[KFKT-2108];北京医学奖励基金会项目[YXJL-2020-0276-0009]。

摘　　要：目的探讨黄芩苷对糖尿病(DM)模型大鼠肾功能的保护作用及作用机制。方法将30只雄性SD大鼠随机分为空白对照组[A组,1%羧甲基纤维素钠(CMC-Na)],模型对照组(B组,1%CMC-Na),黄芩苷组(C组,30 mg/kg黄芩苷),各10只。除A组外,B组和C组大鼠一次性腹腔注射链脲佐菌素(STZ)30 mg/kg,以复制糖尿病模型大鼠。建模成功后均灌胃相应药物或1%CMC-Na,每日1次,连续14周。测定大鼠体质量和肾脏质量;检测大鼠空腹血糖(FBG)、24 h尿蛋白定量、肌酐(Cr)、尿素氮(BUN);采用酶联免疫吸附(ELISA)法检测大鼠体内超氧化物歧化酶(SOD)、丙二醛(MDA)水平;分别采用苏木精-伊红(HE)、天狼星红(Sirius Red)、马松(Masson)染色,观察肾组织形态学变化;采用免疫组化法检测肾组织中层粘连蛋白(LN)含量;采用免疫印迹(Western blot)法检测肾组织中转化生长因子β_(1)(TGF-β_(1))蛋白及哺乳动物雷帕霉素靶蛋白(mTOR)表达水平。结果与B组比较,C组大鼠FBG及肾脏质量指数均显著降低,24 h尿蛋白定量、Cr、BUN、MDA、LN水平均显著降低,SOD含量显著升高(P<0.05);肾组织纤维化程度显著减轻(P<0.05);TGF-β1及mTOR蛋白表达水平均显著降低(P<0.05)。结论黄芩苷可抑制DM模型大鼠肾脏细胞外基质积聚,降低氧化应激水平,延缓糖尿病肾病的进程,其作用机制可能与抑制TGF-β_(1)/mTOR信号通路有关。Objective To investigate the protective effect and mechanism of baicalin on renal function in diabetes mellitus(DM)rats.Methods Thirty male SD rats were randomly divided into the blank control group[group A,1%methylcellulose sodium(CMC-Na)],model control group(group B,1%CMC-Na)and baicalin group(group C,30 mg/kg baicalin),with 10 rats in each group.Except those in group A,rats in groups B and C were given a one-time intraperitoneal injection of 30 mg/kg of streptozotocin(STZ)to replicate DM model rats.After successful modeling,corresponding drugs or 1%CMC-Na were administered orally once a day for 14 weeks.The body mass and renal mass of rats were measured.The fasting blood glucose(FBG),24 h urine protein content,creatinine(Cr)and blood urea nitrogen(BUN)were measured.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in rats were detected by the enzyme-linked immunosorbent assay(ELISA).The morphological changes of renal tissue were observed by haematoxylin-eosin(HE)staining,Sirius Red staining,and Masson staining.The content of laminin(LN)in renal tissue was detected by immunohistochemistry.The expression of transforming growth factorβ_(1)(TGF-β_(1))protein and mammalian target of sirolimus(mTOR)in renal tissue was detected by the Western blot.Results Compared with those in group B,the FBG and renal mass index of rats were significantly lower,the content of 24 h urinary protein content,Cr,BUN MDA and LN were significantly lower,while the content of SOD was significantly higher in group C(P<0.05).Compared with those in group B,the degree of renal fibrosis in group C significantly reduced(P<0.05),and the expression levels of TGF-β1 and mTOR protein in group C were significantly lower(P<0.05).Conclusion Baicalin can inhibit the accumulation of extracellular matrix and the level of oxidative stress in the kidney of DM model rats,and delay the development of diabetic nephropathy.Its mechanism may be related to the inhibition of TGF-β_(1)/mTOR signaling pathway.

关 键 词：黄芩苷 糖尿病 转化生长因子β_(1) 哺乳动物雷帕霉素靶蛋白 氧化应激 肾功能 作用机制 

分 类 号：R965[医药卫生—药理学] R977.15[医药卫生—药学]