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目的 探讨白术内酯Ⅰ(ATL1)对糖尿病肾病(DN)大鼠肾纤维化的影响及作用机制。方法 建立DN大鼠模型,SD大鼠随机分为对照(CT)组、DN模型(DN)组、ATL1低、高剂量(ATL1 L、H)组、ATL1 H+Ad-NC组、ATL1 H+Ad-YAP组;给药结束后,各组称重,血糖仪检测空腹血糖(FBG),试剂盒测定肾功能指标,苏木素-伊红(HE)染色观察肾组织病理学,Masson染色检测肾纤维化及胶原容积分数(CVF),免疫组化检测转化生长因子(TGF)-β1、母亲对抗全能者同系物(Smad)2蛋白表达,Western印迹检测Hippo-YAP信号通路相关蛋白表达。结果 相比CT组,DN组肾小球增大,基底膜增厚,肾小管扩张,大量炎性细胞浸润,呈现肾纤维化,体质量及磷酸化(p)-巨噬细胞刺激因子(MST)1/MST1、p-大肿瘤抑制因子(LATS)1/LATS1蛋白表达明显下降,FBG、肾功能指标、CVF及TGF-β1、Smad2、p-YAP/YAP蛋白表达明显升高(P<0.05);相比DN组,ATL1 L、H组肾组织病变逐渐明显减轻,体质量及p-MST1/MST1、p-LATS1/LATS1蛋白表达明显升高,FBG、肾功能指标、CVF及TGF-β1、Smad2、p-YAP/YAP蛋白表达下降,且呈明显剂量依赖性(P<0.05);相比ATL1 H+Ad-NC组,ATL1 H+Ad-YAP组肾组织病理损伤加重,体质量及p-MST1/MST1、p-LATS1/LATS1蛋白表达明显下降,FBG、肾功能指标、CVF及TGF-β1、Smad2、p-YAP/YAP蛋白表达明显升高(P<0.05)。结论 ATL1可能通过抑制Hippo-YAP信号通路改善DN大鼠肾纤维化。
Abstract:1 Samsu N.Diabetic nephropathy:challenges in pathogenesis,diagnosis,and treatment[J].Biomed Res Int,2021;2021(1):1-17.
2 Hung PH,Hsu YC,Chen TH,et al.Recent advances in diabetic kidney diseases:from kidney injury to kidney fibrosis[J].Int J Mol Sci,2021;22(21):1-20.
3 Guo Y,Xiao Y,Zhu H,et al.Inhibition of proliferation-linked signaling cascades with atractylenolide Ⅰ reduces myofibroblastic phenotype and renal fibrosis[J].Biochem Pharmacol,2021;183(1):1-40.
4 Zhang J,Xu Q,Ren F,et al.Inhibition of YAP activation attenuates renal injury and fibrosis in angiotensin Ⅱ hypertensive mice[J].Can J Physiol Pharmacol,2021;99(10):1000-6.
5 应勤丽,黄月碧,杨秀翠,等.圣草酚通过抑制TGF-β1/Smad3信号通路改善糖尿病肾病大鼠肾纤维化[J].中国免疫学杂志,2023;39(4):693-7.
6 吴英智.白术内酯Ⅰ通过抑制纤维合成保护心肾综合征大鼠心肾功能[D].广州:南方医科大学,2018.
7 Li X,Lu L,Hou W,et al.Epigenetics in the pathogenesis of diabetic nephropathy[J].Acta Biochim Biophys Sin(Shanghai),2022;54(2):163-72.
8 Sagoo MK,Gnudi L.Diabetic nephropathy:an overview[J].Methods Mol Biol,2020;2067(1):3-7.
9 Deng M,Chen H,Long J,et al.Atractylenolides(Ⅰ,Ⅱ,and Ⅲ):a review of their pharmacology and pharmacokinetics[J].Arch Pharm Res,2021;44(7):633-54.
10 Xie Z,Lin M,He X,et al.Chemical constitution,pharmacological effects and the underlying mechanism of atractylenolides:a review[J].Molecules,2023;28(10):3987-4010.
11 Wang L,Wang HL,Liu TT,et al.TGF-beta as a master regulator of diabetic nephropathy[J].Int J Mol Sci,2021;22(15):7881-99.
12 Lodyga M,Hinz B.TGF-β1-a truly transforming growth factor in fibrosis and immunity[J].Semin Cell Dev Biol,2020;101(1):123-39.
13 Hu HH,Chen DQ,Wang YN,et al.New insights into TGF-β/Smad signaling in tissue fibrosis[J].Chem Biol Interact,2018;292(1):76-83.
14 Ma TT,Meng XM.TGF-β/Smad and renal fibrosis[J].Adv Exp Med Biol,2019;1165(1):347-64.
15 Ibar C,Irvine KD.Integration of Hippo-YAP signaling with metabolism[J].Dev Cell,2020;54(2):256-67.
16 Mia MM,Singh MK.New insights into Hippo/YAP signaling in fibrotic diseases[J].Cells,2022;11(13):2065-86.
17 Guo Y,Luo J,Zou H,et al.Context-dependent transcriptional regulations of YAP/TAZ in cancer[J].Cancer Lett,2022;527(1):164-73.
18 Patel S,Tang J,Overstreet JM,et al.Rac-GTPase promotes fibrotic TGF-β1 signaling and chronic kidney disease via EGFR,p53,and Hippo/YAP/TAZ pathways[J].FASEB J,2019;33(9):9797-810.
基本信息:
中图分类号:R285.5
引用信息:
[1]胡曼莉,陈杰,刘小婷,等.白术内酯Ⅰ调节Hippo-YAP信号通路对糖尿病肾病大鼠肾纤维化的影响及作用机制[J].中国老年学杂志,2026,46(15):2826-2830.
基金信息:
武汉市医学科研项目(WX19Z38)
2026-08-10
2026-08-10