目的 探讨血清鸢尾素在腺嘌呤诱导的慢性肾病(chronic kidney disease,CKD)大鼠模型中的表达和变化,及鸢尾素与其相关通路在CKD肾纤维化中的作用.方法 采用简单随机法将20只雄性SD大鼠分为对照组和模型组(CKD组),每组各10只.观察比较建模后第2、4周末两组大鼠的生化指标、血清鸢尾素和血清BMP7水平与肾脏病理改变及肾纤维化程度,并检测其肾脏组织的α-平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)、Ⅰ 型胶原(collagen type Ⅰ,Col-Ⅰ)、骨形成蛋白 7(bone morphogenetic protein 7,BMP7)、Smadl 蛋白和信使RNA(messenger RNA,mRNA)表达水平.结果 与对照组比较,CKD组在建模后第2、4周末的血清肌酐、血清尿素氮和24 h蛋白尿定量均升高(P＜0.05),α-SMA、Col-Ⅰ蛋白及mRNA表达水平均增加(P＜0.05),血清鸢尾素和血清BMP7均降低(P＜0.05),BMP7、Smad1蛋白和mRNA表达水平均降低(P＜0.05).与建模后第2周末比较,CKD组在建模后第4周末的血清肌酐、血清尿素氮和24 h蛋白尿定量均升高(P＜0.05),α-SMA、Col-Ⅰ蛋白及mRNA表达水平均增加(P＜0.05),血清鸢尾素和血清BMP7均降低(P＜0.05),BMP7、Smad1蛋白和mRNA表达水平均降低(P＜0.05).CKD组的肾组织结构比对照组出现明显结构紊乱及胶原纤维沉积,并随时间进展程度加重.血清鸢尾素与α-SMA、Col-Ⅰ均呈负相关(r=-0.917、-0.902,P＜0.001),与血清BMP7呈正相关(r=0.842,P＜0.001);肾脏组织BMP7与Smad1呈正相关(r=0.884,P＜0.001).目的基因热图分析结果显示,与对照组比较,CKD组中BMP7及鸢尾素的前体Ⅲ型纤连蛋白结构域蛋白5表达下调,α-SMA和Col-Ⅰ表达上调;Ⅲ型纤连蛋白结构域蛋白5与BMP7呈正相关,与Col-Ⅰ、α-SMA呈负相关.结论 鸢尾素可通过调节BMP7/Smad1信号通路参与腺嘌吟诱导的CKD大鼠肾纤维化的发生发展,这将为肾纤维化的防治提供新思路.
Expression and significance of irisin in rats model with adenine-induced chronic kidney disease
Objective To explore the expression and changes of serum irisin in adenine-induced chronic kidney disease(CKD)model,and the role of irisin and related pathway in CKD renal fibrosis.Methods Twenty male SD rats were randomly divided into a control group and a model group(CKD group)using a simple randomization method,with 10 rats in each group.At the end of the 2nd and 4th week,biochemical indicators,serum irisin and serum bone morphogenetic protein 7(BMP7)levels,renal pathologic changes and interstitial fibrosis of renal tubules were measured in two groups of rats.The protein expression levels and messenger RNA(mRNA)expression levels of alpha-smooth muscle actin(α-SMA),collagen type Ⅰ(Col-Ⅰ),BMP7,and Smad1 in rat kidney tissue were detected and compared.Results Compared with the control group at the end of the 2nd and 4th week,the CKD group showed that the serum creatinine(Scr),serum urea nitrogen(BUN),and 24-hour urinary protein level were increased(P＜0.05),the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased(P＜0.05),while the serum irisin and serum BMP7 were decreased(P＜0.05),the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced(P＜0.05).Compared with the end of the 2nd week,the CKD group at the end of the 4th week showed that the serum Scr,serum BUN,and 24-hour urinary protein level were increased(P＜0.05),the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased(P＜0.05),while the serum irisin and serum BMP7 were decreased(P＜0.05),the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced(P＜0.05).Compared to the control group,the renal tissue structure of the CKD group showed significant structural disorders and interstitial fibrosis of the renal tissue,which worsened over time.Serum irisin was negatively correlated withα-SMA and Col-Ⅰ(r=-0.917,-0.902,P＜0.001)respectively,while serum irisin was positively correlated with serum BMP7(r=0.842,P＜0.001);Kidney tissue BMP7 was positively correlated with Smad1(r=0.884,P＜0.001).The cluster heat map showed that compared with the control group,BMP7 and recombinant fibronectin type Ⅲ domain containing were significantly decreased,α-SMA and Col-Ⅰ were significantly increased in CKD group;recombinant fibronectin type Ⅲdomain containing were positively correlated with BMP7,and negatively correlated with α-SMA and Col-Ⅰ.Conclusions irisin may be involved in the process of renal fibrosis in adenine-induced CKD via the BMP7/Smad1 axis.This will provide new ideas for the prevention and treatment of renal fibrosis.
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