RhoA和ROCK蛋白在高脂饮食幼鼠肾小球中的表达及其意义

doi:10.13481/j.1671-587x.20190621

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (06): 1315-1319.doi: 10.13481/j.1671-587x.20190621

RhoA和ROCK蛋白在高脂饮食幼鼠肾小球中的表达及其意义

汤淼¹, 艾浩², 李晓明^1,3

1. 锦州医科大学组织学与胚胎学教研室, 辽宁锦州 121001;
2. 辽宁省卵泡发育与生殖健康重点实验室, 辽宁锦州 121001;
3. 广东药科大学组织学与胚胎学教研室, 广东广州 510006

收稿日期:2019-01-15 出版日期:2019-12-05 发布日期:2019-12-05
通讯作者: 李晓明,教授,硕士研究生导师(Tel:0416-3999231,E-mail:lixiaoming68327@163.com) E-mail:lixiaoming68327@163.com
作者简介:汤淼(1988-),女,辽宁省锦州市人,在读医学硕士,主要从事肾脏发育和肾脏疾病方面的研究。
基金资助:
辽宁省科技厅自然科学基金资助课题（20170540373）；辽宁省锦州市科技局科学技术计划项目资助课题（16B1G35）

Expressions of RhoA and ROCK proteins in glomeruli of young mice fed with high-fat diet and their significances

TANG Miao¹, AI Hao², LI Xiaoming^1,3

1. Department of Histology and Embryology, Jinzhou Mediacal University, Jinzhou 121001, China;
2. Key Laboratory of Follicular Development and Reproductive Health, Jinzhou Mediacal University, Jinzhou 121001, China;
3. Department of Histology and Embryology, Guangdong Pharmaceutical University, Guangzhou 510006, China

Received:2019-01-15 Online:2019-12-05 Published:2019-12-05

摘要/Abstract

摘要： 目的：探讨RhoA和ROCK蛋白在高脂饮食（HFD） C57BL/6J幼鼠肾小球中的表达，阐明RhoA/ROCK通路是否与HFD诱导的肾小球损伤有关。方法：36只雄性C57BL/6J幼鼠随机分为正常对照组和HFD组，每组18只，正常对照组幼鼠给予标准饲料，HFD组幼鼠给予高脂饲料，分别饲养12周。检测幼鼠体质量和血清总胆固醇（TC）及甘油三酯（TG）水平。HE染色、PAS染色和Masson染色观察2组幼鼠肾组织病理形态表现、肾小球系膜和基底膜相对面积以及肾间质纤维组织相对面积，免疫组织化学法检测2组幼鼠肾小球中RhoA和ROCK蛋白表达水平，免疫蛋白印迹法检测2组幼鼠肾小球中RhoA、ROCK和Vimentin蛋白的表达水平。结果：与正常对照组比较，HFD组小鼠体质量、血清TC和TG水平明显升高（P<0.01）。HE染色，HFD组小鼠肾小球内出现明显脂肪变性；PAS染色，HFD组小鼠出现肾小球系膜基质轻度增生；Masson染色，HFD组小鼠肾小球内蓝色胶原纤维染色物质比正常对照组增多；与正常对照组比较，HFD组小鼠肾小球系膜和基底膜相对面积明显增加（P<0.05），肾间质纤维组织相对面积增加（P<0.05）；免疫组织化学检测，与正常对照组比较，HFD组幼鼠肾小球中RhoA的ROCK蛋白表达水平升高（P<0.05）；免疫蛋白印迹法检测，与正常对照组比较，HFD组幼鼠肾小球中RhoA、ROCK和Vimentin蛋白表达水平升高（P<0.05）。结论：给予HFD的C57BL/6J小鼠肾小球中RhoA和ROCK蛋白高表达可能是诱发肾小球损伤的原因之一。

关键词: 高脂饮食, 肾小球, RhoA蛋白, ROCK 蛋白

Abstract: Objective: To investigate the expressions of RhoA and ROCK proteins in glomeruli of the C57BL/6J young mice fed with high-fat diet(HFD),and to elucidate whether the RhoA/ROCK pathwaywas related to glomerular injuryinduced by HFD. Methods: Thirty-six male C57BL/6J mice were randomly divided into normal control group and HFD group,and there were 18 mice in each group.The mice in normal control group were given standard diet,and the mice in HFD group were given HFD;they were fed for 12 weeks.The body weights and the serum levels of total cholesterol (TC) and triglyceride (TG) of the young mice in two groups were measured.HE staining,PAS staining and Masson staining were used to observe the pathomorphology of kidney tissue,the relative areas of mesangial membrane and basement membrane and renal interstitial fibrous tissue of the young mice in two groups were detected;immunohistochemical method was used to detect the expression levels of RhoA and ROCK in glomeruli of the young mice in two groups.The expression levels of RhoA,ROCK and vimentin proteins in glomeruli of the young mice in two groups were detected by Western blotting method. Results: Compared with normal control group,the body weight,the serum TC and TG levels of the young mice in HFD group were significantly increased (P<0.01).The HE staining results showed obvious fatty degeneration in the glomeruli of the young mice in HFD group;the PAS staining results showed mild proliferation of glomerular mesangial matrix of the young mice in HFD group;the Masson staining results showed that blue collagen fibers in glomeruli of the mice in HFD group were more abundant than those of the mice in normal control group.Compared with normal control group,the relative area of mesangial membrane and basement membrane of the young mice in HFD group was significantly increased (P<0.05),and the relative area of renal interstitial fibrous tissue was increased (P<0.05).Compared with normal control group,the expression levels of RhoA and ROCK proteins in the glomeruli of the young mice in HFD group were increased (P<0.05);the expression levels of RhoA,ROCK and Vimentin in the glomeruli of the young mice in HFD group were increased (P<0.05). Conclusion: The high expressions of RhoA and ROCK proteins in glomeruli of the C57BL/6J mice fed with HFD may be one of the causes of glomerular injury.

Key words: high-fat diet, glomerulus, RhoA proein, ROCK protein

中图分类号:

R589.2

汤淼, 艾浩, 李晓明. RhoA和ROCK蛋白在高脂饮食幼鼠肾小球中的表达及其意义[J]. 吉林大学学报(医学版), 2019, 45(06): 1315-1319.

TANG Miao, AI Hao, LI Xiaoming. Expressions of RhoA and ROCK proteins in glomeruli of young mice fed with high-fat diet and their significances[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1315-1319.

参考文献

[1] AN YN,LI Y,WANG X Y,et al.Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats[J].Lipids Health Dis,2018,17(1):276.
[2] YU O M,BROWN J H.G protein-coupled receptor and RhoA-stimulated transcriptional responses: links to inflammation,differentiation,and cell proliferation[J].Mol Pharmacol,2015,88(1):171-180.
[3] MONAGHAN-BENSON E,WITTCHEN E S,DOERSCHUK CM,et al.A Rnd3/p190RhoGAP pathway regulates RhoA activity in idiopathic pulmonary fibrosis fibroblasts[J].Mol Biol Cell,2018,29(18):2165-2175.
[4] MANICKAM N,PATEL M,GRIENDLING K K,et al.RhoA/Rho kinase mediates TGF-β1-induced kidney myofibroblast activation through Poldip2/Nox4-derived reactive oxygen species[J].Am J Physiol Renal Physiol,2014,307(2):F159-F171.
[5] FENG S,ZOU L,WANG H J,et al.RhoA/ROCK-2 pathway inhibition and tight junction protein upregulation by catalpol suppresses lipopolysaccaride-induced disruption of blood-brain barrier permeability[J].Molecules,2018,23(9):E2371.
[6] TAKIYAMA Y,SERA T,NAKAMURA M,et al.Impacts of diabetes and an SGLT2 inhibitor on the glomerular number and volume in db/db mice,as estimated by synchrotron radiation micro-CT at spring-8[J].EBioMedicine,2018,36:329-346.
[7] WU W,HU W,HAN W B,et al.Inhibition of Akt/mTOR/p70S6K signaling activity with huangkui capsule alleviates the early glomerular pathological changes in diabetic nephropathy[J].Front Pharmacol,2018,9:443.
[8] BAO J F,SHI Y F,TAO M,et,al.Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy[J].Clin Sci,2018,132(21):2299-2322.
[9] KOVESDY C P,FURTH S L,ZOCCALI C.Obesity and kidney disease: hidden consequences of the epidemic[J].Braz J Med Biol Res,2017,50(5):e6075.
[10] BARTON M,SOROKIN A.Endothelin and the glomerulus in chronic kidney disease[J].Semin Nephrol,2015,35(2):156-167.
[11] NIU H L,LI Y,LI H B,et al.Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity[J].Sci Rep,2016,6:20171.
[12] JERUSCHKE S,BÜSCHER A K,OH J,et al.Protective effects of the mTOR inhibitor everolimus on cytoskeletal injury in human podocytes are mediated by RhoA signaling[J].PLoS One,2013,8(2):e55980.
[13] BABA I,EGI Y,UTSUMI H,et al.Inhibitory effects of fasudil on renal interstitial fibrosis induced by unilateral ureteral obstruction[J].Mol Med Rep,2015,12(6): 8010-8020.
[14] 刘恒.Rho/Rho激酶信号通路和肝细胞生长因子在2型糖尿病大鼠肾病中的作用[D].石家庄:河北医科大学,2012.
[15] XIE X,CHEN Q,TAO J.Astaxanthin promotes Nrf2/ARE signaling to inhibit HG-induced renal fibrosis in GMCs[J].Mar Drugs,2018,16(4):117.
[16] 谌祖江.芪丹地黄汤抑制糖尿病肾病肾脏纤维化的作用和机制研究[D].广州:南方医科大学,2018.
[17] KOLAVENNU V,ZENG L X,PENG H,et al.Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy independent of glucose control[J].Diabetes,2008,57(3):714-723.
[18] 马东蔚,王秋月,马小羽.法舒地尔通过Rho/ROCK信号通路对高糖培养人肾小球系膜细胞炎症反应及纤维化的影响[J].中华内科杂志,2011,50(7):580-584.
[19] PENG F F,WU D C,GAO B,et al.RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease[J].Diabetes,2008,57(6):1683-1692.
[20] DANIELSSON F,PETERSON M K,CALDEIRA ARAUJO H,et al.Vimentin diversity in health and disease[J].Cells,2018,7(10): E147.
[21] SUBATHRA M,KORRAPATI M,HOWELL L A,et al. Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells[J].Am J Physiol Renal Physiol,2015,309(3):F204-F215.
[22] 沈健,臧东钰,李晓明.高脂饮食诱导的C57BL/6J幼鼠肾足细胞中Synaptodin的表达及意义[J].解放军医学院学报,2015,36(9):940-943.

RhoA和ROCK蛋白在高脂饮食幼鼠肾小球中的表达及其意义

Expressions of RhoA and ROCK proteins in glomeruli of young mice fed with high-fat diet and their significances

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