中药药理与临床2025，Vol.41Issue(11)：45-50,6.
益气养阴活血方调控VDR/DDIT4/mTOR信号通路促进细胞自噬缓解糖尿病肾病
Mechanism of Yiqi Yangyin Huoxue Formula in Upregulating Autophagy to Alleviate Diabetic Nephropathy by Regulating VDR/DDIT4/mTOR Signaling Pathway
摘要
Abstract
Objective:To explore the renal protective mechanism of Yiqi Yangyin Huoxue Formula(YYHF,益气养阴活血方)in diabetic nephrop-athy(DN)rats by activating the vitamin D receptor(VDR)/DNA damage-inducible transcript 4(DDIT4)/mammalian target of rapamycin(mTOR)signaling pathway and subsequently upregulating autophagy.Methods:SPF male SD rats were randomly divided into a normal con-trol group and a modeling group and were fed a regular diet or a high-fat and high-sugar diet,respectively.The DN model was induced in the modeling group through a single intraperitoneal injection of streptozotocin(STZ)at a dose of 35 mg/kg.After modeling,rats were randomly divided into a model control group,a positive control group receiving valsartan at a dose of 8.33 mg/kg(valsartan group),and groups receiv-ing YYHF at doses of 11.0 g/kg(YYHF-11 group)and 22.0 g/kg(YYHF-22 group),respectively.After four weeks of continuous drug ad-ministration,24-hour urine total protein(24 h-UTP)was measured for each rat.Blood from the abdominal aorta was collected for biochemical analysis,including levels of serum albumin(Alb),alanine aminotransferase(ALT),blood urea nitrogen(BUN),serum creatinine(SCr),glucose(GLU),total cholesterol(CHO),and triglyceride(TG).Histopathological changes in kidney tissue were observed using HE stai-ning.The protein and mRNA expression levels of VDR,DDIT4,mTOR(phosphorylated mTOR,p-mTOR),unc-51-like autophagy-activating kinase 1(ULK1),and autophagy-related factor Beclin-1 in kidney tissue were assessed using Western blotting and PCR,respectively.Re-sults:Compared with the normal control group,the model control group showed significantly elevated levels of 24 h-UTP,SCr,BUN,GLU,CHO,and TG(P<0.05),as well as significant renal histopathological damage.The mRNA expression levels of Vdr,Ddit4,Ulk1,and Beclin1 in kidney cells were significantly downregulated(P<0.05),while mtor mRNA expression was significantly upregulated(P<0.05).The pro-tein expression levels of VDR,DDIT4,p-mTOR/mTOR,ULK1,and Beclin-1 were significantly downregulated in kidney cells(P<0.05),while the protein expression levels of mTOR and p-mTOR were significantly upregulated(P<0.05).Compared with the model control group,both the YYHF-11 group and YYHF-22 group showed significantly reduced levels of 24 h-UTP,SCr,BUN,GLU,CHO,and TG in kidney cells(P<0.05),as well as alleviated renal histopathological damage.The mRNA expression levels of Vdr,Ddit4,Ulk1,and Beclin1 in kidney cells were significantly upregulated(P<0.05),while mtor mRNA expression was significantly downregulated(P<0.05).The protein expression levels of VDR,DDIT4,p-mTOR/mTOR,ULK1,and Beclin-1 were significantly upregulated(P<0.05),while mTOR and p-mTOR protein ex-pression levels were significantly downregulated(P<0.05).Conclusion:YYHF can upregulate renal cell autophagy and restore the homeo-static balance of renal cells by activating the VDR/DDIT4/mTOR signaling pathway,thereby alleviating renal histopathological damage and protecting renal function.关键词
益气养阴活血方/糖尿病肾病/细胞自噬/维生素D受体/DNA损伤诱导转录因子4/哺乳动物雷帕霉素靶蛋白信号通路Key words
Yiqi Yangyin Huoxue Formula/Diabetic nephropathy/Autophagy/Vitamin D receptor(VDR)/DNA damage-inducible transcript 4(DDIT4)/mammalian target of rapamycin(mTOR)signaling pathway引用本文复制引用
樊艳敏,宋纯东,姜浩然,方虹,季晗舒,王旭..益气养阴活血方调控VDR/DDIT4/mTOR信号通路促进细胞自噬缓解糖尿病肾病[J].中药药理与临床,2025,41(11):45-50,6.基金项目
国家自然科学基金面上项目(编号:82074493) （编号:82074493）
河南省卫生健康委员会河南省中医药科学研究专项重点课题(编号:2024ZY1002) （编号:2024ZY1002）
河南省中医药学科领军人才项目(豫卫中医函(2021)8号) （豫卫中医函(2021）
河南省卫健委国家中医临床研究基地科研专项(编号:2022JDZX003) （编号:2022JDZX003）
河南省中医药科学研究重大专项(编号:2023ZYZD02) （编号:2023ZYZD02）
河南省"双一流"创建工程(编号:HSRP-DFCTCM-2023-3-07). （编号:HSRP-DFCTCM-2023-3-07）
