肾上腺髓质素在肾间质纤维化实验小鼠肾脏细胞增殖中的作用

目的探讨肾上腺髓质素(ADM)在梗阻性肾病中对细胞增殖的影响。方法采用单侧输尿管结扎(UUO)的方法制备梗阻性肾病模型,给予缬沙坦10mg·kg-1·d-1灌胃治疗,采用免疫组化及RT-PCR检测野生小鼠(WT)和肾上腺髓质素基因敲除小鼠(AMKO)肾脏增殖细胞核抗原(PCNA)、Ⅲ型胶原(ColⅢ)和转化生长因子β1(TGF-β1)的表达。结果野生UUO组小鼠与假手术组相比PCNA阳性细胞数增加,缬沙坦能减少PCNA阳性细胞数。与野生小鼠比较,AMKO假手术组PCNA阳性细胞明显增多,AMKO-UUO组尤为明显,缬沙坦能减少AMKO-UUO组的PCNA阳性细胞数,Ⅲ型胶原和TGF-β1的蛋白表达与mRNA在AM-KO-UUO组明显上调,可被缬沙坦拮抗。结论肾上腺髓质素在UUO介导的肾间质病变的细胞增殖过程中有着重要的作用。

Effects of adrenomedullin on the cell proliferation in renal interstitial fibrosis mice induced by unilateral ureteral obstruction

Aim To investigate the role of adrenomedullin on cell proliferation in renal interstitial fibrosis mice. Method Renal interstitial fibrosis model was induced with unilateral ureteral obstruction (UUO) and valsartan(10 mg·kg·d-1) was given by gavage. Immunohistochemistry and RT-PCR were used to detect expressions of PCNA, Col Ⅲ and TGF-β_1 in the kidney of wild type (WT) and adrenomedullin knockout (AMKO) +/-mice. Results The number of PCNA positive cells was increased in WT-UUO group compared with WT sham group and was partially reduced by Valsartan in WT-UUOV group. AMKO group showed higher expression of PCNA than WT group, and it increased more remarkably in AMKO-UUO mice but was reduced by Valsaltan in AMKO-UUOV group. Expressions of Col Ⅲ andTGF-β_1 were upregulated in AMKO-UUO mice, and this change was inhibited by Valsaltan.Conclusion Adrenomedullin play an important role in the process of cell proliferation in renal interstitial pathological changes by UUO.