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肾上腺髓质素对大鼠Thy-1肾炎肾小球系膜细胞增生和Ⅳ型胶原、纤连蛋白沉积的影响

Effect of Adrenomedullin on the Proliferation of Mesangial Cells and Accumulation of Type Ⅳ Collagen and Fibronectin in the Glomeruli of Rats with Anti-thy1 Glomerulonephritis

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【作者】 戴璐刘学光赵仲华张志刚郭慕依

【Author】 DAI Lu, LIU Xue-guang, ZHAO Zhong-hua, ZHANG Zhi-gang,GUO Mu-yi (Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China)

【机构】 复旦大学上海医学院病理学系复旦大学上海医学院病理学系 上海200032上海200032上海200032

【摘要】 目的研究肾上腺髓质素(adreomedullin,AM)对大鼠Thy-1系膜增生性肾炎肾小球系膜细胞增生和细胞外基质合成的影响,为其用于防治肾小球疾病提供实验依据。方法自制兔抗大鼠Thy-1多克隆抗体,建立大鼠Thy-1系膜增生性肾炎模型,随机分为对照组、模型组和AM治疗组。分别于3、5、7d处死大鼠,每组至少处死6只,取其肾脏,分别作组织切片细胞核苏木精染色以及增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)免疫组化染色,应用图像分析技术行肾小球细胞数、PCNA阳性细胞数和α-SMA表达强度检测。经抽提肾组织蛋白,用Western Blot法检测肾组织Ⅳ型胶原(ColⅣ)和纤连蛋白(FN)的表达。结果与对照组相比,模型组和治疗组3、5、7d时,肾小球细胞数、PCNA阳性细胞数及α-SMA表达强度均明显增高(P<0.05或P<0.01);于3d时,治疗组的上述各指标均较模型组显著降低(P<0.01),而5、7d时则差异不显著。与对照组相比,模型组和治疗组3、5、7d时,肾组织ColⅣ、FN表达明显增强(P<0.01);于3d时,治疗组肾组织ColⅣ、FN表达均显著降低(P<0.01),而5、7d时则差异不明显。结论AM对大鼠Thy-1肾炎早期肾小球细胞增生及基质合成有一定抑制作用。

【Abstract】 Purpose To study the effect of adrenomedullin(AM) on the proliferation of mesangial cells and accumulation of extracellular matrix(ECM) in the glomeruli of rats with anti-thy1 glomerulonephritis to provide experimental basis for treating human glomerulopathy. Methods Anti-thy1 glomerulonephritic rats were produced by injecting rabbit polyclonal antibody against thymic Thy-1 antigen of rat.Experimental rats were randomly divided into control group, model group and AM treatment group. Renal samples were taken from more than 6 sacrificed rats for each group at 3, 5, 7 day. Renal tissue sections were stained by hematoxylin staining to detect cell nuclei, and by immunohistochemistry to detect the expressions of proliferating cell nucleus antigen(PCNA) and α-smooth muscle actin(α-SMA). Protein was extracted from renal tissue to detect the expressions of type Ⅳ collagen (Col Ⅳ) and fibronectin(FN). Results Compared with control group, the total cell number,PCNA positive cell number and the α-SMA staining intensity in model group and AM treatment group increased significantly (P<0.05 or P<0.01) from day 3 to day 7. They all decreased significantly in AM treatment group at 3 d, but were not changed statistically at 5 d and 7 d.Compared to model group (P< 0.01 ). Compared with control group, the expressions of Col Ⅳ and FN in model group and AM treatment group increased significantly (P<0.01) from day 3 to day 7. Both of them decreased significantly in treatment group,but not changed statistically at 5 d and 7 d, compared to model group(P<0.01) at day 3. Conclusions Adrenomedullin could partly inhibit mesangial cells proliferation and glomerular ECM accumulation in early phase of rat anti-thy1 glomerulonephritis in vivo.

【基金】 国家自然科学基金资助项目(30270614)
  • 【文献出处】 复旦学报(医学版) ,Journal of Shanghai Medica(University) , 编辑部邮箱 ,2005年06期
  • 【分类号】R692.3
  • 【下载频次】170
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