姜黄素通过TGF-β/Smads信号通路对肾缺血再灌注后肾小管间质纤维化抑制作用

Curcumin inhibits tubulointerstitial fibrosis after renal ischemia-reperfusion through TGF-β/Smads signaling pathway

摘要:

目的： 探究姜黄素通过TGF-β/Smads信号通路对肾缺血再灌注后肾小管间质纤维化的抑制作用。方法： 将40只健康SD大鼠按随机数字表法平均分为假手术组、模型组、低剂量组和高剂量组。使用夹闭法松开肾蒂的方法复制肾缺血再灌注大鼠模型。检测血清中血清肌酐（serum creatinine，Scr）和尿素氮（urea nitrogen，BUN）水平、肾组织胶原含量、肾组织的病理变化以及肾脏中转化生长因子-β1（transforming growth factor β1,TGF-β1）、Smad3和Smad7蛋白表达水平。结果： 假手术组肾小管形态正常，模型组肾小管间质呈现明显的病理变化，低剂量组和高剂量组肾小管间质纤维病理变化明显改善，且高剂量组改善程度高于低剂量组；模型组的肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3明显高于假手术组，Smad7明显低于假手术组（P<0.05）；低剂量组和高剂量组肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3均明显低于模型组，Smad7明显高于模型组（P<0.05）；高剂量组肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3评分明显低于低剂量组，Smad7明显高于低剂量组（P<0.05）。结论： 姜黄素对肾缺血再灌注后肾小管间质纤维化具有抑制作用，其作用机制可能为抑制TGF-β/Smad信号转导通路。

Abstract:

Objective: To explore the inhibitory effect of curcumin inhibits tubulointerstitial fibrosis after renal ischemia-reperfusion through TGF-β/Smads signaling pathway. Methods: Forty healthy SD rats were randomly divided into sham operation group, model group, low dose group and high dose group. Clamped and loosened renal pedicle to make renal ischemia-reperfusion rat model. Serum creatinine (Scr) and urea nitrogen (BUN) levels, collagen content in kidney tissue, pathological changes of kidney tissue and expression of TGF-β1, Smad3 and Smad7 protein in kidney were measured. Results: The shape of renal tubules was normal in sham-operation group, and there were significant pathological changes of renal tubular fibers in model group. The pathological changes of tubulointerstitial fibers in low dose group and high dose group were significantly improved, and the improvement degree in high dose group was higher than that in low dose group. The renal tubulointerstitial fibrosis score, Scr, BUN, collagen content, TGF-β1 and Smad3 in the model group were significantly higher than those in the sham operation group, and Smad7 was significantly lower than that in the sham operation group (P<0.05). The tubulointerstitial fibrosis score, Scr, BUN, collagen content, TGF-β1 and Smad3 in low dose group and high dose group were significantly lower than those in model group, and Smad7 was significantly higher than that in model group (P<0.05). The scores of renal tubulointerstitial fibrosis, Scr, BUN, collagen content, TGF-β1 and Smad3 in high dose group were significantly lower than those in low dose group, and Smad7 was significantly higher than that in low dose group (P<0.05). Conclusion: Curcumin can inhibit tubulointerstitial fibrosis after renal ischemia-reperfusion, and the mechanism may be inhibition of TGF-β/Smad signal transduction pathway.