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研究Sirt1活化剂对单侧输尿管结扎导致的小鼠肾间质纤维化及TGF-β1/CTGF信号通路的影响。CD-1小鼠随机分为假手术组(Sham)、单侧输尿管结扎组(unilateral ureteral obstruction,UUO)和UUO+SRT1720(Sirt1活化剂)组(SRT1720)。Masson染色后光镜下观察肾小管间质病变面积;分别用Western blot和Real-time PCR检测Sirt1及纤维化相关因子Col1、α-SMA、TIMP-1、PAI-1蛋白质和m RNA表达水平;TUNEL检测细胞凋亡程度,同时检测凋亡相关因子Bcl-2/Bax的变化;检测SOD、MDA、GPx、GSH水平以示氧化应激变化。与Sham组相比,UUO组显示肾间质纤维化病变面积显著升高(P<0.01);Sirt1水平及活性显著下降;TGF-β1/CTGF水平、纤维化相关因子表达及凋亡水平显著上升;氧化应激水平显著升高(P<0.01)。SRT1720干预能够显著降低UUO引起的肾间质纤维化病变面积(P<0.05),同时改善TGF-β1/CTGF水平、纤维化相关因子及凋亡水平(P<0.01),显著降低肾脏氧化应激水平(P<0.01)。以上说明,Sirt1活化剂SRT1720能显著改善肾间质纤维化水平,该作用可能是通过TGF-β1/CTGF信号通路的抑制和氧化应激实现的。
To investigate the effect of Sirt1 activator on renal interstitial fibrosis and TGF-β1 / CTGF signaling in mice with unilateral ureteral obstruction. CD-1 mice were randomly divided into sham group, unilateral ureteral obstruction (UUO) and UUO + SRT1720 (Sirt1 activator) group (SRT1720). Masson staining was used to observe the area of tubulointerstitial lesions. The expressions of Sirt1, fibronectin, Col1, a-SMA, TIMP-1 and PAI-1 protein and m RNA were detected by Western blot and Real- TUNEL was used to detect the degree of apoptosis. Meanwhile, the apoptosis-related factor Bcl-2 / Bax was detected. The levels of SOD, MDA, GPx and GSH were detected to show the changes of oxidative stress. Compared with Sham group, UUO group showed a significant increase in the area of renal interstitial fibrosis (P <0.01), Sirt1 level and activity decreased significantly, TGF-β1 / CTGF level, fibrosis-related factor expression and apoptosis increased significantly ; Oxidative stress was significantly increased (P <0.01). SRT1720 intervention could significantly reduce the area of renal interstitial fibrosis induced by UUO (P <0.05), and at the same time improve the level of TGF-β1 / CTGF, fibrosis-related factors and apoptosis (P <0.01) Level (P <0.01). The above description, Sirt1 activator SRT1720 can significantly improve the level of renal interstitial fibrosis, the effect may be through TGF-β1 / CTGF signaling inhibition and oxidative stress.