牵牛子多糖治疗膜性肾病的组分效应关系及其免疫调节机制研究

At present, the incidence of membrane nephropathy (MN) has not been effectively controlled in China, especially in Northeast China the number of cases has increased dramatically. MN has become one of the major diseases seriously affecting the physical and mental health, economic, social development and stability of people who live in China especially in Northeast China. In the early stage, we got the result that semen pharbitidis polysaccharides have the obvious treatment effect on MN. At this present stage, by determining the optimum conditions and by qualitative and quantitative analysis for preparation of semen pharbitidis polysaccharides, this project was carried out for the first time in investigating the functional mechanism of semen pharbitidis polysaccharides on MN in rats induced by cationic bovine serum albumin (C-BSA) based on its immunomodulatory and anti-oxidation activities, to investigate antioxidant indexes and immunologic factors related to immune inflammatory mediators such as NF-κB from multiple levels including serum, protein level and mRNA levels. The study on the treatment of MN by semen pharbitidis polysaccharides is initiated. By means of further in-depth mechanism study of the project, the immune regulation and antioxidation regulation mechanism on the treatment of MN rats by semen pharbitidis polysaccharides could be clarified. It could also deepen the understanding of the mechanism on occurrence, development and prognosis of MN and its relevant targets. Also, it can reveal the scientific connotation of semen pharbitidis efficacy, and develop an innovative drug for the treatment of MN with a good efficacy but low toxic side effects, in order to provide an important scientific basis for making full use of the semen pharbitidis.

目前，我国膜性肾病的发病率尚未得到有效控制，尤其东北地区患病人数急剧增加，该病已成为严重影响我国特别是东北地区人们身心健康和经济、社会发展和稳定的主要疾病之一。本项目在前期已确定牵牛子多糖具有明显的治疗膜性肾病作用的基础上，通过确定最佳工艺条件及定性定量制备牵牛子多糖，首次基于免疫调节及抗氧化作用探讨牵牛子多糖对阳离子化小牛血清白蛋白(C-BSA)所致大鼠膜性肾病的作用机制，从多个层次水平对抗氧化指标及NF-κB等免疫炎症介质相关免疫因子等指标进行血清、蛋白水平、mRNA水平测试。有关牵牛子多糖治疗膜性肾病的研究尚为首创，通过本项目的深入的机制研究可阐明牵牛子多糖治疗膜性肾病大鼠的免疫调节与抗氧化调节机制，深化对膜性肾病发生、发展和转归机制及相关靶点的认识，同时可揭示牵牛子功效的科学内涵，并可为研制出疗效好毒副作用低的治疗膜性肾病的创新药物，为充分利用牵牛子丰富的药用资源提供重要科学依据。

膜性肾病(MN)是慢性肾病的常见病理类型之一，严重可发展成尿毒症，我国MN发病率尚未得到有效控制，尤其东北地区患病人数急剧增加。而市面上的免疫抑制药物，都有或多或少或短期或长期的毒性作用，部分中药研究虽也取得了一定进展，但成分变化不易控制，成分结构不清楚，机制仍然尚不十分清楚。本项目在前期已确定牵牛子有效部位的基础上，完成了牵牛子多糖提取等相关的工艺参数研究，包括牵牛子总多糖的特征识别、含量测定研究、多糖结构研究，为牵牛子多糖的特征识别提供参考依据。完成了从多层次多水平对对照组、模型组及给药各组大鼠关于一般药效学，及抗氧化指标及NF-κB等免疫炎症介质相关免疫因子等指标在血清、mRNA水平、蛋白水平的机制研究。结果表明，牵牛子多糖可通过下调MN大鼠肾组织中NF-κB等指标mRNA表达水平，降低血清和肾组织中以上指标因子的含量及蛋白表达。从而可能分别调控各个炎性细胞因子的转录，抑制相关炎症反应的发生发展；抑制MN大鼠肾小球免疫复合物沉积，并阻止免疫细胞异常分泌；抑制系膜细胞增殖、基质积聚和硬化；抑制肾脏中性粒细胞，嗜碱性粒细胞和T细胞的聚集和活化；抑制成纤维细胞增生，改善MN大鼠肾间质的纤维化现象，从而达到对MN大鼠的免疫调节作用。本项目研究结果深化了对牵牛子多糖功能及治疗MN药效作用机理的认识，同时揭示了牵牛子功效的科学内涵，并可为牵牛子多糖对于具有水肿症状的其他类型肾病的研究提供了科研方向。