Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice
Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice
复制标题
DOI：
10.1177/0961203308098989
复制
发表时间：
2009-05-01
期刊：
影响因子：
2.6
通讯作者：
Kon, Y.
中科院分区：
文献类型：
--
作者：
Ichii, O.;Konno, A.;Kon, Y.
女性B6 MRLc 1（82-100）同源小鼠比雄性小鼠发生更严重的自身免疫性肾小球肾炎（AGN）。我们评估了性腺切除对这些小鼠AGN发病机制的影响。将1月龄雄性和雌性小鼠分为假手术组（SG）和去性腺组（GG），8月龄时观察病理变化。SG雌性动物的脾脏和胸腺重量、血清总IgG和自身抗体水平、肾小球损伤评分以及IgG和CD 3阳性肾小球百分比均高于SG雄性动物。性腺切除术的效果男性比女性更明显。GG雄性动物的脾脏和胸腺重量、尿白蛋白排泄、肾小球损伤评分、IgG和CD 3阳性肾小球百分比以及脾脏中的CD 3阳性面积均显著高于SG雄性动物。除SG雄性动物外，在所有动物的胸腺皮质和髓质中均观察到CD 3阳性细胞。肾脏中活性Fc γ受体（Fcgr）3与抑制性Fcgr 2b的表达比率，我们先前已证明其对B6的发病机制有很大影响。GG雄性的MRLc 1（82-100）显著高于SG雄性。这些结果表明，AGN发病机制的差异主要是由于男性性激素的抑制作用。Lupus（2009）18，491-500.
Female B6. MRLc1(82-100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6. MRLc1(82-100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones. Lupus (2009) 18, 491-500.