姜黄素对醛固酮诱导肾间质纤维化的保护作用

Protective effect of curcumin on aldosterone-induced tubulointerstitial fibrosis in rats

目的探讨姜黄素对醛固酮诱导肾纤维化的保护作用和机制。方法雄性SD大鼠行左侧单肾切除后给予醛固酮处理诱导肾间质纤维化,同时分别给予姜黄素、安体舒通以及姜黄素和安体舒通联合处理。留取24 h尿采用ELISA法检测尿糖皮质激素诱导蛋白激酶(SGK1)、转化生长因子-β1(TGF-β1)、IL-6和TNF-α排泄情况;组织病理切片采用Masson染色观察肾组织纤维化程度,免疫组化和RT-PCR观察各组TGF-β1、结缔组织生长因子(CTGF)和血清糖皮质激素诱导蛋白激酶(SGK1)的表达情况。结果醛固酮能显著增加尿TGF-β1、IL-6和TNF-α水平(P<0.01),姜黄素和安体舒通均能显著减少上述因子的排泄水平(P<0.01),二者合用具有协调作用。病理组织学结果显示,醛固酮可明显促进肾小管间质纤维化以及TGF-β1、CTGF和SGK1等致炎致纤维化因子表达,姜黄素和安体舒通能显著拮抗醛固酮的促炎促纤维化效应,二者合用有协同效应。结论姜黄素能通过抑制致炎致纤维化因子表达而有效拮抗醛固酮诱导的肾间质纤维化。

Objective It is to investigate the protective effect of curcumin on aldosterone-induced rat tubulointerstitial fibrosis and its related mechanism.Methods Left uni-nephrectomized SD rats were used to exacerbate tubulointerstitial fibrosis by treating with aldosterone.Meanwhile,these rats were administrated with curcumin,spironolactone,and both curcumin and spironolactone respectively.24h urine was collected to assay urinary TGF-β1,IL-6 and TNF-α levels by ELISA method.Masson straining were employed to assay the degree of tubulointerstitial fibrosis,RT-PCR and immunohistology were used to detect the expression of TGF-β1,CTGF and SGK1 in renal tissue in every group.Results Aldosterone can significantly increase urinary TGF-β1,IL-6 and TNF-α levels（P0.01）,which were markedly inhibited by the addition of curcumin and spironolactone（P0.01）,and the combination of them had better effect.The pathological results showed aldosterone could exacerbate tubulointerstitial fibrosis,increase the expressions of TGF-β1,CTGF and SGK1 in renal tissue,which were markedly inhibited by the treatment of curcumin and spironolactone.A significant cooperativity was observed in rat renal tissue using both curcumin and spironolactone treatment.Conclusion Aldosterone-induced tubulointerstitial fibrosis can be antagonized by inhibition of profibrotic and proinflammatory factors expression with curcumin.