姜黄素对db/db小鼠肾组织p-STAT3及IκB蛋白的影响

Effect of curcumin on the expression of p-STAT3 and IκB in db/db mice

目的:观察姜黄素对db/db小鼠糖尿病肾病的疗效,并探讨其可能的作用机制。方法:雌性db/db小鼠10只,随机分为模型组和姜黄素治疗组,5只db/m小鼠为正常对照组,姜黄素治疗组予以姜黄素200 mg/(kg·d)连续灌胃18周。实验结束时,尾静脉采血测血糖,ELISA检测小鼠24 h尿蛋白,PAS染色观察小鼠肾组织病理改变,免疫组织化学检测IV型胶原以及纤连蛋白(fibronectin,FN)在肾组织的表达,Western印迹检测磷酸化的信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)及IκB在肾组织的表达。结果:与db/m小鼠比较,db/db小鼠体型肥胖,血糖明显升高,伴有大量蛋白尿;病理改变为肾小球肥大,系膜区扩张,基膜增厚,细胞外基质(extracellular matrix,ECM)合成增加;Western印迹检测肾组织中磷酸化的STAT3表达增加,IκB表达减少。与db/db小鼠比较,姜黄素治疗后明显降低db/db小鼠24 h尿蛋白,减少肾组织中IV型胶原以及FN的表达,抑制STAT3磷酸化及IκB降解。结论:姜黄素可以减少2型糖尿病模型db/db小鼠的蛋白尿,减轻肾小球硬化,其作用机制可能与抑制STAT3磷酸化及IκB降解有关。

Objective: To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism. Methods: Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg·d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3(STAT3) and IκB in the kidney. Results: Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney. Conclusion: Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.