内皮素在大鼠系膜增生性肾小球肾炎中的表达

Glomerular expression of endothelin-1 in anti-Thy1. 1 glomerulonephritis

目的研究内皮素－１（ＥＴ－１）在系膜增生性肾小球肾炎（ＭｓＰＧＮ）模型中的表达。方法以小鼠抗大鼠Ｔｈｙ１．１单克隆抗体单次尾静脉注射诱导的大鼠ＭｓＰＧＮ模型，病理观察分析该模型的系膜细胞和系膜基质增生； Ｎｏｒｔｈｅｒｎ杂交分析肾小球前内皮素（ｐｐＥＴ－１） ｍＲＮＡ表达水平；放射免疫分析（ＲＩＡ）测定肾小球ＥＴ－１蛋白水平。结果在大鼠ＭｓＰＧＮ模型中，第２ ｄ系膜细胞溶解消失，第４ ｄ系膜细胞增生，第６ ｄ系膜细胞明显增生伴系膜基质增生。 ＭｓＰＧＮ大鼠肾小球ｐｐＥＴ－１ｍＲＮＡ表达上调，于第 ４ ｄ的表达趋势最强。肾小球 ＥＴ－ １蛋白分别于第 ２ ｄ、第 ６ ｄ两次明显升高［（ ８７．１３± ２０． １６）ｎｇ／ｇ，（１００． １９± １４． １６）ｎｇ／ｇ］，与对照组［（４６．５０±４． ２８）ｎｇ／ｇ］比较，差异有显著性意义（Ｐ＜０．０５）。结论在ＭｓＰＧＮ模型中，伴随着系膜细胞和系膜基质增生，肾小球产生的ＥＴ－１增加，提示ＥＴ－１可能参与了体内系膜细胞和系膜基质增生。

Objective To investigate the expression of endothelin-1 (ET-1) in mesangioproliferative glomerulonephritis (MsPGN) in rats. Methods MsPGN rats were induced by a single intravenous injection of monoclonal anti-thy1. 1 antibody. Glomerular lesions including mesangial cell proliferation and mesangial matrix expansion were observed pathologically. Preproendothelin-1 (ppET-1) mRNA expression in glomeruli were analyzed by Northern blot hybridization. Concentration of ET-1 in glomeruli were measured with radioimmunoassay (RIA). Results in MsPGN rats, mesangial cells dissolved at day 2, proliferated at day 4, proliferated obviously with mesangial matrix expansion at day 6. In parallel with mesangial cell proliferation and mesangial matrix expansion, glomerular ppET-1 mRNA expression was up-regulated with its dominance at day 4. ET-1 protein content in glomeruli was elevated at day 2(87. 13 ±0. 16) ng/g, day 6 (100. 19 ±4. 16) ng/g respectively, compared to control group (46. 50±4. 28) ng/g, P < 0. 05. Conclusions in MsPGN, glomerular ET-1 production increases in association with mesangial cell proliferation and mesangial matrix expansion. ET-1 may be involved in the process of mesangial cell proliferation and mesangial matrix expansion in vivo.