道地中药温莪术治疗肾纤维化药效机制的代谢组学研究

Renal fibrosis is the inevitable common pathway of virtually all progressive kidney diseases to end-stage renal failure. Thus preventing and delaying the renal fibrosis become the key point to the prevention of chronic kidney disease progression to the end-stage renal failure. Curcuma wenyujin is the genuine traditional Chinese medicine (TCM) in south Zhejiang, which plays a notable curative effect in kidney disease. The theory of TCM on the therapeutic effect of Curcuma wenyujin simply rests on the experience summary and macroscopic description, lacking of the scientific experiment interpretation and validation. Metabonomics, an emerging technique in recent years, exhibits the soul of systems biology and has found widespread applications in many research areas including drug efficacy. It has been becoming a promisingly novel approach in the systematic studies of TCM. We have carried out some studies using the metabolomics approach. This project intends to collect the serum, urine and kidney tissue samples from rats of the sham operation, unilateral ureteral obstruction model, and treatment groups to study the metabolic trajectory and the related metabolic pathways, and to find the metabolic biomarkers using the metabonomics approach in combination with several other complementary methods including clinical chemistry, immunohistochemistry, and histopathology. The aims are to speculate the dynamic response of the endogenous metabolism and to understand from a whole the pharmic effect and mechanism of curcuma wenyujin on renal fibrosis. Furthermore, the project will develop novel analytical method for overall evaluation of drug efficacy and for action mechanism of curcuma wenyujin, and provide experimental basis for TCM preventing renal fibrosis.

肾纤维化是所有肾脏疾病进展到终末期肾衰竭的共同通路，阻止和延缓肾纤维化成为防止慢性肾病进展到终末期肾衰竭的关键。温莪术是浙南传统的道地中药，在“治肾防硬”方面疗效显著。中医理论对温莪术的治疗作用往往仅停留在经验的总结和宏观的描述，缺乏科学实验的解释和验证。代谢组学研究的整体性思想和中药的多成分及体内多靶点特征正好相统一，成为中医药研究的重要方法。项目组已应用代谢组学技术开展了不少研究，本项目拟收集单侧输尿管梗阻后不同周期假手术组、模型组、温莪术治疗组和阳性药物组的大鼠的血清、尿液和肾组织样品，应用代谢组学技术研究代谢模式的变化规律和相关代谢调控通路，寻找生物标志物。同时，结合经典的生化分析、免疫组化、病理切片检查，相互补充、相互佐证，从整体上阐述温莪术对肾纤维化代谢通路的调控作用与机制，为温莪术的药效作用整体评价和机制研究提供新的分析方法，为中医药防治肾纤维化提供实验依据。