天然产物研究与开发 ›› 2020, Vol. 32 ›› Issue (10): 1637-1643.doi: 10.16333/j.1001-6880.2020.10.002

• 研究论文 • 上一篇    下一篇

柚皮素通过下调RhoA/ROCK信号通路改善糖尿病肾病小鼠肾纤维化

谢发江1,冉茂霞2,冯健3*,李燕3,李家富3,邓莉4   

  1. 1达州市中心医院心血管内科;2达州市中心医院肾病内科,达州 635000;3西南医科大学附属医院心血管内科;4西南医科大学附属医院风湿免疫科,泸州 646000

  • 出版日期:2020-10-28 发布日期:2020-10-29
  • 基金资助:
    国家自然科学基金(31300946);泸州市-川医大联合课题(2015LZCYD-S03(7/7))

Naringin ameliorates fibrosis via down-regulating RhoA/ROCK signaling pathway in diabetic nephropathy mice

XIE Fa-jiang1,RAN Mao-xia2,FENG Jian3*,LI Yan3,LI Jia-fu3,DENG Li4   

  1. 1Department of cardiology,Dazhou Central Hospital;2Department of Nephrology,Dazhou Central Hospital,Dazhou 635000,China; 3Department of cardiology,the Affiliated Hospital of Southwest Medical University;4Department of Rheumatology and Immunology,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China 
  • Online:2020-10-28 Published:2020-10-29

摘要: 为探讨柚皮素对糖尿病肾病(diabetic nephropathy,DN)小鼠肾纤维化的影响及其机制。将32只C57BL/6小鼠随机分为正常组、模型组、柚皮素组、法舒地尔组。DN模型复制成功后分别予柚皮素及法舒地尔处理,正常组、模型组予生理盐水对照,连续12周,处死小鼠,观察血肌酐(serum creatinine,Scr)、24 h尿蛋白定量(24-hour urinary protein quantity,24 h Upro)、血糖、体重的变化;HE及Masson染色观察肾脏形态学改变;免疫组化观察肾脏RhoA、ROCK1、ROCK2、I型胶原蛋白(type-I collagen,Col1)、III型胶原蛋白(type-III collagen,Col3)的水平;Western blot测定肾脏RhoA、ROCK1、ROCK2、p-MYPT1、层粘连蛋白(laminin,LN)、纤连蛋白(fibronectin,FN)的水平。结果显示肾脏形态学观察可见正常组间质少许胶原纤维,模型组间质大量胶原纤维,处理组间质少量胶原纤维。与正常组相比,模型组24 h Upro、Scr升高(P<0.05);与模型组相比,处理组24 h Upro、Scr降低(P<0.05),血糖、体重差异无统计学意义(P>0.05)。与正常组相比,模型组RhoA、ROCK1、ROCK2、Col1、Col3、p-MYPT1 Thr853、LN、FN的水平升高(P<0.05);与模型组比较,处理组RhoA、ROCK1、ROCK2、Col1、Col3、p-MYPT1 Thr853、LN、FN的水平降低(P<0.05)。与柚皮素组相比,法舒地尔组各指标差异无统计学显著性(P>0.05)。柚皮素具有改善DN小鼠肾纤维化的作用,其机制可能与下调RhoA/ROCK信号通路有关。


关键词: 糖尿病肾病, 肾纤维化, 柚皮素, RhoA/ROCK信号通路

Abstract:

To investigate the effect of naringin on renal fibrosis in diabetic nephropathy mice and its′ specific mechanism.C57BL/6 mice (n=32) were randomly divided into normal group,diabetic nephropathy group,naringin group and fasuldil group.After the successful establishment of diabetic nephropathy (DN) model,the naringin group mice were given naringin suspension by gavage,the fasuldil group mice were given fasudil by intraperitoneal injection,simultaneously,the normal and diabetic nephropathy group were given isopyknic normal saline.After 12 weeks of intervention,all mice were sacrificed and the level changes of serum creatinine (Scr),24-hour urinary protein (24 h Upro),blood glucose and body weight were observed.HE and Masson staining were used to observe renal morphological changes.The protein expressions of RhoA,ROCK1,ROCK2,type-I collagen (Col1) and type-III collagen (Col3) in renal tissues were tested by immunohistochemical(IHC) staining.And Western blot was applied to detected the protein levels of RhoA,ROCK1,ROCK2,p-MYPT1,Laminin (LN),Fibronectin (FN) in renal tissue.HE and Masson staining showed a little collagen fiber in the renal interstitium of normal group,a large amount of collagen fiber in diabetic nephropathy group and a small amount of collagen fiber in naringin and fasuldil group.Compared with normal group,the levels of 24 h Upro and Scr were increased in diabetic nephropathy group(P<0.05);Compared with diabetic nephropathy group,the levels of 24 h Upro and Scr were decreased in naringin and fasuldil group(P<0.05).However,no statistically difference in blood glucose and body weight between the treatment groups and diabetic nephropathy group was observed (P>0.05).Compared with the normal group,the protein levels of RhoA,ROCK1,ROCK2,Col 1,Col 3,p-MYPT1 Thr853,LN and FN were increased in the diabetic nephropathy group (P<0.05);And compared with the diabetic nephropathy group,these protein levels were markedly decreased in the naringin and fasuldil group(P<0.05).In addition,there was no statistically significant difference in each index between naringin and fasuldil group.Naringin could ameliorate the renal fibrosis in DN mice,which is possibly related to the down-regulation of RhoA/ROCK signaling pathway.

Key words: diabetic nephropathy, renal fibrosis, naringin, RhoA/ROCK signaling pathway

中图分类号:  R589.1 R587.1