摘要
目的:探讨大黄附子汤(DFD)在体内调控尿酸性肾病(UN)模型肾组织JNK/Bcl-2信号通路而改善肾小管/间质损伤的机制。方法:第1-14天腺嘌呤混悬液灌胃诱导大鼠建立UN模型,第15-35天分别用DFD和别嘌呤醇(AP)干预,此期间,每隔3d,给予模型和药物干预组大鼠腺嘌呤,以维持肾功能稳定。观察各组大鼠的血清、尿液、肾小管上皮细胞凋亡等相关指标;检测肾组织JNK/Bcl-2信号通路相关分子以及转化生长因子β1(TGF-β1)的蛋白相对表达量。结果:经灌胃给予腺嘌呤14d后,大鼠SUA、BUN、Scr明显升高,达到鼠类高尿酸和肾衰竭水平。在药物干预3周后,用药组的血清和尿液各项指标明显降低,肾小管上皮细胞凋亡及间质纤维化程度减轻,肾组织c-Jun氨基末端激酶磷酸化(p-JNK)、B细胞淋巴瘤基因2磷酸化(p-Bcl-2)、活化型半胱天冬酶-3(cleavedCaspase-3)以及TGF-β1蛋白表达下调。DFD组的各项指标优于AP组。结论:DFD通过调节肾组织JNK/Bcl-2信号通路,减少肾组织内TGF-β1表达和肾小管上皮细胞凋亡,改善肾间质纤维化,最终延缓UN进展。
Objective： To explore the mechanism of Dahuangfuzi Decoction （DFD） in improving renal tubulo-interstitial injury via JNK/Bcl-2 signaling pathway in uric acid nephropathy （UN） model rats. Methods： Rats were intragastric administrated by adenine suspension to establish UN model from day 1 to 14. Model rats were administrated of DFD and aUopurinol solution （AP） respectively from day 15 to 35, during which time, rats in model and intervention groups were administrated of adenine suspension every 3 days to stabilize the renal function. Serum and urinary parameters, as well as tubular epithelial cells apoptosis and related index were detected. Besides, the relative protein expressions of associated molecular in JNK/Bcl-2 pathway of renal tissues and transforming growth factor-β1 （TGF-β1） were detected. Results： SUA, BUN and Scr were increased significantly in model rats after the intragastric administration of adenine suspension for 14 days. Moreover, the model rats appeared human-like high urin acid and renal failure level.After 3-week medical intervention, DFD and AP reduced serum and urinary parameters, ameliorated tubular epithelial ceils apoptosis and interstitial fibrosis, as well as down-regulated the protein expressions of phosphorylated Jun N-terminal kinases （p-JNK）, phosphorylated Bcl-2 （p-Bcl-2）, cleaved caspase-3 and TGF-β1. DFD was more effective than AP. Conclusion： DFD reduced TGF-β1 protein expression and tubular epithelial cells apoptosis, as well as alleviated renal interstitial fibrosis via regulating JNK/Bcl-2 singaling pathway, eventually improving UN.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第5期1351-1356,I0006,共7页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
江苏省高校优势学科建设工程资助项目~~
作者简介
通讯作者：孙伟，南京市汉中路115号江苏省中医院肾内科，邮编：210029，电话：025—86617141，E-mail：sunyb59@yahoo．com．cn
