罗格列酮对慢性环孢素肾病大鼠肾间质纤维化的保护作用

Rosiglitazone reduces renal interstitial fibrosis in chronic cyclosporine nephropathy rats

目的探讨罗格列酮（RGZ）对环孢素A（CsA）所致慢性环孢素肾病（CCN）大鼠肾间质纤维化的保护作用。方法28只健康雄性SD大鼠被随机分成4组：（1）对照组（n=6）：低盐饮食（LSD）；（2）RGZ组（n=6）：LSD＋RGZ（5mg·kg-1·d-1）；（3）CsA组（n=8）：LSD＋CsA（15mg·kg-1·d-1），（4）RGZ＋CsA组（n=8）：LSD＋CsA（15mg·kg-1·d-1）＋RGZ（5mg·kg-1·d-1）。实时荧光定量PCR观察骨调素（OPN）及RANTES表达量；RT-PCR法检测MMP．9和TIMP．1的表达量；常规染色观察肾脏病理改变。结果RGZ可改善CsA所致大鼠肌酐清除率的降低[（0．253±0．027）比（0．133±0．018）ml／min，P〈0．05】；降低CCN大鼠肾间质单个核细胞浸润【（22．50±2．71）比（30．38±3．11），P〈0．05】；减轻肾间质纤维化程度[（1．707±0．019）比（2．335±0．022），P〈0．05]。与CsA组比较，RGZ＋CsA组大鼠肾组织中OPN和RANTESmRNA表达量和MMP-9、TIMP-1mRNA表达量降低（均P〈0．05）。结论RGZ可能通过下调趋化因子OPN、RANTES及MMP-9、TIMP-1的表达，改善CCN大鼠肾问质纤维化。

Objective To investigate the effect of rosiglitazone on renal interstitial fibrosis in chronic cyclosporine nephropathy （CCN） rats. Methods Twenty-eight rats were randomly assigned to control group, rosiglitazone （RGZ, 5 mg·kg-1·d-1） group, cyclosporine A（CsA, 15 mg·kg-1·d-1） group, rosiglitazone （5 mg·kg-1·d-1） ＋CsA group. Real-time PCR and RT-PCR methods were used to investigate the expressions of OPN, RANTES on the 14th day and MMP-9, TIMP-1 on the 35th day in kidney of CCN respectively. Results In comparison with control group, the expressions of OPN, RANTES, MMP-9, TIMP-1 in CsA and RGZ＋CsA groups were increased （P〈 0.05）. In comparison with the CsA group , the expressions of OPN, RANTES, MMP-9, TIMP-1 in CsA＋RGZ group significantly decreased （P〈0.05）. Conclusion Rosiglitazone may protect renal tissue after CCN by decreasing expressions of OPN, RANTES, MMP-9, TIPM-1.