罗格列酮对环孢素A所致肾毒性保护作用的机制
Effects of rosiglitazone on cyclosporine A-related renal toxicity in rats
董吉 1唐琳 1刘章锁 1程根阳 1权松霞1
作者信息
- 1. 郑州大学第一附属医院肾内科,河南,郑州,450052
- 折叠
摘要
目的:观察罗格列酮(RGZ)对环孢素A(CsA)所致肾组织炎细胞浸润及肾间质纤维化的作用,探讨RGZ对CsA肾病(CCN)的保护作用.方法:将28只健康雄性SD大鼠随机分成:①对照组(n=6),LSD;②RGZ组(n=6),LSD+RGZ[5 mg/(kg·d)];③CsA组(n=8),LSD+CsA[15 mg/(kg·d)],④RGZ+CsA组(n=8),LSD+CsA[15 mg/(kg·d)]+RGZ(5 mg/(kg·d)).在实验开始后的2 wk及5 wk处死大鼠,分别用免疫组化方法检测CD68和ColⅣ,RT-PCR方法检测MMP-9和TIMP-1的表达量;HE,Masson染色观察肾脏病理改变.结果:与对照组相比,CsA组及RGZ+CsA组CD68,ColⅣ,MMP-9,TIMP-1的表达均增高,肾小管间质单个核细胞浸润数及肾间质纤维化程度显著增加,且CsA组显著高于RGZ+CsA组.RGZ组无明显变化.结论:RGZ可显著降低CsA对肾脏的毒性作用,其机制部分是通过降低CCN大鼠CD68,ColⅣ,MMP-9,TIMP-1的表达,从而改善肾间质纤维化.
Abstract
AIM: To investigate protective effect of rosiglitazone on cyclosporine A-related renal tissue renal interstitial fibrosis in rats. METHODS: Twenty-eight rats were randomly assigned to normal group (n=6,LSD),rosiglitazone [5 mg/( kg · d)] group (n=6,RGZ),cyclosporine A [15 mg/(kg · d)] group (n =8,CsA),and cyclosporine A [ 15 mg/( kg · d) ] and rosiglitazone [5 mg/(kg· d) ] group (n=8,RGZ + CsA). Immu-nohistochemistry and RT-PCR were used to investigate the pathological changes of the kidneys and the expression of CD68,Col Ⅳ,MMP-9 and TIMP-1 at the 2nd week and the 5th week in the rats in each group. RESULTS: In comparison with that in normal group,the expression of CD68,ColⅣ,MMP-9 and TIMP-1 in CsA group and CsA + RGZ group markedly increased ( P < 0.05). In comparison with that in CsA group,the expression of CD68,Col Ⅳ,MMP-9 and TIMP-1 significantly decreased in CsA + RGZ group (P<0.05). CONCLUSIOM: Rosiglitazone alleviates CsA-related renal interstitial fibrosis by decreasing the expression of CD68,ColⅣ,MMP-9 and TIMP-1.
关键词
环孢菌素A/罗格列酮/CD68/ColⅣ/明胶酶B/金属蛋白酶1组织抑制剂/肾间质纤维化Key words
cyclosporine A/rosiglitazone/CD68/ColⅣ/gelati-nase B/tissue inhibitor of metalloproteinase-1/renal interstitial fibrosis引用本文复制引用
基金项目
河南省科技攻关项目(0324410084)
河南省杰出青年科学基金(74100510006)
出版年
2009
NETL
NSTL
维普
万方数据