CGRP对UUO小鼠肾组织间质纤维化与炎性因子表达的干预作用

Intervention effects of CGRP on renal interstitial fibrosis and expression of inflammatory cytokines in mice with unilateral ureteral obstruction

目的探讨CGRP对小鼠单侧输尿管梗阻(UUO)模型肾间质纤维化的影响。方法选择雄性小鼠36只,建立小鼠UUO模型,前2 d治疗组和模型组分别每天给予CGRP 1.0 nmol·kg^(-1)·d^(-1)和同等量0.9%氯化钠溶液静脉注射。观察模型第14天肾小管损害百分比、肾间质纤维化程度、肾间质α-SMA平滑肌肌动蛋白、肾间质巨噬细胞数,单核细胞趋化蛋白-1(MCP-1)以及F4/80 mRNA的表达。结果 CGRP显著减轻肾小管损害和肾间质纤维化(P<0.05);治疗组肾间质巨噬细胞数F4/80和肾间质α-SMA表达显著低于模型组(P<0.05);CGRP显著抑制MCP-1以及F4/80 mRNA的表达(P<0.05)。结论 CGRP减少小鼠UUO模型肾间质巨噬细胞浸润、降低MCP-1以及F4/80 mRNA表达、抑制α-SMA的表达,从而减轻肾间质纤维化。

Objective To investigate the effects of calcitonin gene-related peptide （ CGRP ） on renal interstitial fibrosis and expression of Inflammatory cytokines in mice with unilateral ureteral obstruction （UUO）.Methods The animal models with UUO were established in 36 mice.The mice in treatment group were given CGRP 1.0nmol · kg-1 · d-1 by intravenous injection,however,the mice in model group were given equivalent 0.9% sodium chloride solution by intravenous injection.The mice in both groups were sacrificed after 14-day administration,then the percentage of renal tubular lesion ,the extent of renal interstitial fibrosis , number of renal interstitial macrophage cells , the expression levels of renal interstitial expression of α-smooth muscle actin （α-SMA）, monocyte chemotactic protein-1 （MCP-1） and F4/80 mRNA were observed and compared between two groups .Results CGRP alleviated significantly renal tubular lesion and renal interstitial fibrosis （P〈0.05 ）.The expression levels of α-SMA and macrophages number in renal interstitial in treatment groups were significantly lower than those in model group （ P 〈0.05）.Moreover CGRP inhibited significantly the expression levels of MCP-1 and F4/80 mRNA （ P 〈0.05）.Conclusion CGRP can reduce macrophage infiltration of mice with UUO ,decrease the expression levels of MCP-1 and F4/80 mRNA,inhibit the expression of α-SMA so as to relieve renal interstitial fibrosis .