子痫前期血清通过Caveolin-1增加肾小球内皮细胞通透性被引量：2

The high expression of caveolin-1 causes the hyperpermeability of human glomerular endothelial cells in preeclampsia patients

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摘要目的:探讨子痫前期血清对肾小球内皮细胞(HRGEC)通透性的影响以及caveolin-1表达在子痫前期血清影响HRGEC通透性过程中的作用。方法:采用原代培养的肾小球内皮细胞,实验分组:正常妊娠血清培养组(A组),子痫前期血清培养组(B组),子痫前期血清+caveolae蛋白的抑制剂甲基-β-环糊精(MBCD)处理组(C组)。免疫荧光及免疫印迹监测HRGEC caveolin-1蛋白表达;细胞接种transwell小室,Evens-blue检测HRGEC单层细胞对大分子蛋白通透性改变;Western blot法检测caveolin-1表达。结果:子痫前期血清明显促进单层HRGEC对大分子蛋白的通透性与caveolin-1表达(P<0.05),MBCD能拮抗子痫前期血清促单层HRGEC对大分子蛋白的通透性与caveolin-1表达的作用。结论:子痫前期患者血清通过增加caveolin-1蛋白表达促进HRGEC单层细胞对大分子蛋白的通透性,caveolin-1表达异常可能在子痫前期患者蛋白尿形成过程中起重要作用。 Objective： To explore the serum impacts on the permeability of human renal glomerular endothelial cells（ HRGEC） in preeclampsia patients and the function of expressed caveolin-1 on the permeability of HRGEC. Method： To culture the primary HRGEC and observe the position of Caveolin-1 in HRGEC by immunofluorescence. Then culture HRGEC in a device called ＂transwell＂. Three groups were divided： Group A was treated with the serum of normal pregnant when the cells overgrew the whole upper chamber. Group B was treated with the preeclampsia patients serum. Group C was treated with the same preeclampsia serum as the second group and also one caveolae inhibitor- Methyl-beta- cyclodextrinthe（ MBCD） in a suitable concentration. And then test the Evans-bule conjuncted BSA in the lower chamber to reflect the dynamic permeability of HRGEC. Western blot was used to detect the quantity of caveolin-1 expressed by HRGEC after the cells were stimulated by serums of each group for 24 hours. Result： the permeability of HRGEC was significantly enhanced when they were dealt with preeclampsia serum and the inhibitor could reverse them partly（ P 〈0. 05）. The expression of caveolin-1 was highly elevated（ P 〈0. 05）,it was reduced when treated with MBCD（ P 〈0. 05）. Conclusion： High expressed caveolin-1in preeclampsia patients can lead to hyperpermeability of HRGEC,which may play an important role in proteinuria formation in preeclampsia patients.

作者徐钦洋杜菲蒋荣珍

机构地区上海交通大学附属第六人民医院产科重症监护中心妇产科研究所

出处《现代妇产科进展》 CSCD 北大核心 2016年第1期10-13,18,共5页 Progress in Obstetrics and Gynecology

基金国家自然科学基金资助项目(No:81570444) 国家科技部"十二五"支撑计划项目(No:2014BAI05B05) 上海交通大学医学院健康管理研究基金(LY201501)

关键词子痫前期肾小球内皮细胞 CAVEOLIN-1 屏障障碍蛋白尿 Preeclampsia HRGEC Caveolin-1 Barrier dysfunction Proteinuria

分类号 R714.2 [医药卫生—妇产科学]

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参考文献10

1Jiang RZ,Cai J,Zhu Z,et al.Hypoxic trophoblast HMGB1induces endothelial cell hyperpermeability via the TRL-4/caveolin-1 pathway[J].J Immunol,2014,193(10):5000-5012.
2蒋荣珍,滕银成,黄亚绢,Chen Alex F.缺氧小鼠滋养细胞HMGB1通过TLR4增加内皮细胞通透性[J].现代妇产科进展,2014,23(1):13-17. 被引量：1
3Moriyama T,Takei T,Itabashi M,et al.Caveolae may enable albumin to enter human renal glomerular endothelial cells[J].J Cell Biochem,2015,116(6):1060-1069.
4Chen W,Gassner B,Borner S,et al.Atrial natriuretic peptide enhances microvascular albumin permeability by the caveolae-mediated transcellular pathway[J].Cardiovascular Res,2012,93(1):141-151.
5Siddiqui MR,Komarova YA,Vogel SM,et al.Caveolin-1-e NOS signaling promotes p190Rho GAP-A nitration and endothelial permeability[J].J Cell Biol,2011,193(5):841-850.
6Hailstones H,Sleer L,Parton RG,et al.Regulation of caveolin and caveolae by cholesterol in MDCK cells[J].J Lipid Res,1998,39(2):369-379.
7Taniguchi K,Xia L,Goldberg HJ,et al.Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice[J].Diabetes,2013,62(11):3874-3886.
8Moriyama T,Tsuruta Y,Shimizu A,et al.The significance of caveolae in the glomeruli in glomerular disease[J].J Clin Pathol,2011,64(6):504-509.
9Lobysheva I,Rath G,Sekkali B,et al.Moderate caveolin-1downregulation prevents NADPH oxidase-dependent endothelial nitric oxide synthase uncoupling by angiotensin II in endothelial cells[J].Arteriosclerosis,thrombosis,vascular Biol,2011,31(9):2098-2105.
10LI F,Hagaman JR,Kim HS,et al.e NOS deficiency acts through endothelin to aggravate s Flt-1-induced pre-eclampsia-like phenotype[J].J A Society Nephrol,2012,23(4):652-660.

二级参考文献7

1Y. Gu,L.J. Groome,J.S. Alexander,Y. Wang.PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia[J].Placenta.2012(10)
2Wonhwa Lee,Tae Hoon Kim,Sae-Kwang Ku,Kyoung-jin Min,Hyun-Shik Lee,Taeg Kyu Kwon,Jong-Sup Bae.Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models[J].Toxicology and Applied Pharmacology.2012(1)
3Katsuhiko Naruse,Toshiyuki Sado,Taketoshi Noguchi,Taihei Tsunemi,Shozo Yoshida,Juria Akasaka,Natsuki Koike,Hidekazu Oi,Hiroshi Kobayashi.Peripheral RAGE (Receptor for Advanced Glycation Endproducts)-ligands in normal pregnancy and preeclampsia: novel markers of inflammatory response[J].Journal of Reproductive Immunology.2012(2)
4Jiyong Zhang,Hideo K. Takahashi,Keyue Liu,Hidenori Wake,Rui Liu,Tomoko Maruo,Isao Date,Tadashi Yoshino,Aiji Ohtsuka,Shuji Mori,Masahiro Nishibori.Anti-high Mobility Group Box-1 Monoclonal Antibody Protects the Blood–Brain Barrier From Ischemia-Induced Disruption in Rats[J].Stroke A Journal of Cerebral Circulation.2011(5)
5Rachel K. Wolfson,Eddie T. Chiang,Joe G.N. Garcia.HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption[J].Microvascular Research.2010(2)
6X.H. Wang,S.F. Chen,H.M. Jin,R.M. Hu.Differential analyses of angiogenesis and expression of growth factors in micro- and macrovascular endothelial cells of type 2 diabetic rats[J].Life Sciences.2008(7)
7David A. Edelman,Yang Jiang,James G. Tyburski,Robert F. Wilson,Christopher P. Steffes.Lipopolysaccharide activation of pericyte’s Toll-like receptor-4 regulates co-culture permeability[J].The American Journal of Surgery.2007(6)