摘要
目的探讨多西环素对肾间质纤维化的影响及可能机制。方法采用单侧输尿管结扎术(UUO)致肾小管间质纤维化大鼠模型。将72只SD大鼠随机分为假手术组、模型组、多西环素治疗组[8 mg/(kg·d)]。手术后7,14,21 d时分别处死各组中6只大鼠,用免疫组化方法观察大鼠肾组织中转化生长因子-β1(TGF-β1)、基质金属蛋白酶2(MMP-2)表达情况。行HE及Masson染色评定大鼠肾脏的病理情况。结果模型组各时间点MMP-2表达明显低于同期假手术组(P<0.05),多西环素组各时间点MMP-2表达明显低于同期模型组(P<0.05),多西环素组术后14 d及术后21 d低于术后7 d。模型组各时间点TGF-β1表达明显高于同期假手术组(P<0.05),而多西环素组术后7 d TGF-β1表达明显低于同期模型组,多西环素组术后14 d及术后21 d高于术后7 d。结论多西环素在肾小管间质纤维化的早期对肾脏有保护作用。
Objective To investigate the effect of doxycycline on the renal interstitial fibrosis in rats and its possible mechanism. Methods The unilateral ureteral obstruction （ UUO ） was adopted to create the renal tubular interstitial fibrosis model in rats. 72 normal female Sprague-Dawley rats were randomly divided into the sham-operation group, UUO model group and doxycycline treatment [ 8 mg/ （ kg·d ） ] group. 6 rats in each group were respectively sacrificed on 7, 14, 21 d after surgery. Immunohistochemistry was adopted to detect the expression of transforming growth factor-β1 （ TGF-β1 ） and matrix metalloproteinase-2 （ MMP-2 ） in the obstructed renal tissue. The HE staining and the Masson staining were performed to evaluate the renal pathological status in each group. Results The expression of MMP-2 at different time points in the UUO model group was significantly lower than that in the sham-operation group （ P〈0. 05 ） , and the expression of MMP-2 at different time points in the doxycycline group was significantly lower than that in the UUO model group （ P〈0. 05 ） , the expression of MMP-2 on postoperative 14, 21 d in the doxycycline group were lower than that on postoperative 7 d. The expression of TGF-β1 at different time points in the UUO model group was significantly higher than that in the sham-operated group （ P〈0. 05 ） , but the expression of TGF-β1 on postoperative 7 d in the doxycycline group was significantly lower than that in the UUO model group, which on postoperative 14, 21 d in the doxycycline group was significantly higher than that an post-operative 7 d. Conclusion Doxycycline has a protective effect on the early tubulointerstitial fibrosis.
出处
《中国药业》
CAS
2014年第17期7-9,共3页
China Pharmaceuticals
