通脉颗粒治疗嘌呤霉素氨基核苷肾病的药效学研究及机理探讨

【作者】 闫静；

【导师】 李兴广； 李平； 于文明；

【作者基本信息】 北京中医药大学 ， 临床中药学， 2005， 硕士

【摘要】 肾病综合征(Nephropathy Syndrome,NS)是一种对人类健康危害很大以及给家庭、社会带来沉重负担的临床常见病。临床表现有四大特点:大量蛋白尿、低蛋白血症、高脂血症和明显水肿。在临床治疗方面,激素类、免疫抑制剂仍然是目前西药治疗肾病综合征的常用药物,但激素和免疫抑制剂存在较大的毒副作用且用药时间较长。因此,探索新的治疗途径具有重要的临床价值。中医中药在肾脏病的治疗上有其独到之处,目前已经受到国内外学者的广泛关注。开发和研究新型治疗肾病的中药,也是目前学者们研究的热点。 通脉颗粒是广州中医药大学附属医院治疗肾病综合征的有效方剂,为现代中药制剂。为了进一步阐明通脉颗粒的治疗作用,探讨其作用机制,为其临床应用提供更有力的实验依据,我们进行了本实验研究。 本文分为文献综述和实验研究两部分。在文献综述部分,阐述了中医学对肾病综合征的病名、病因病机、常用治法和方药的认识,以及现代医学对肾病综合征的认识,重点对近几年治疗肾病综合征的研究进展进行了归纳。 在实验研究部分,我们进行了以下实验研究:1、制备了嘌呤霉素氨基核苷(puromycin amino nucleoside,PAN)的肾病模型。2、设计了通脉颗粒治疗PAN 肾病的药效学实验。60 只大鼠分正常组、PAN 肾病模型组、通脉颗粒高、中、低剂量组、蒙诺对照组。各治疗组大鼠均给予灌胃给药 30 天(0.1ml/Kg,每日一次)。观察 24h 尿蛋白定量、血清总蛋白、白蛋白、总胆固醇、甘油三酯、血肌酐、尿素氮、体重、肾脏指数等参数及肾脏病理形态学。3、对通脉颗 粒 治 疗 PAN 肾 病 的 机 理 进 行 初 步 探 讨 。 分 析 了 骨 形 成 发 生 蛋 白 ( Bonemorphogenetic protein, BMPs)BMPs 和及其细胞内信号转导蛋白-Smad 蛋白在 PAN 肾病模型组和药物治疗组肾组织中表达的影响。 实验结果表明,PAN 肾病模型造模成功,适合于通脉颗粒的药效学研究。通脉颗粒可以通过抑制 24h 尿蛋白排泄量,调节血浆蛋白代谢和血脂代谢紊乱,保护肾功能,改善肾小球局灶节段硬化和肾间质纤维化等病理改变,抑制肾组织中 BMPⅡ和 Smads1mRNA 的表达,因而对肾病综合征有良好的治疗作用。更多还原

【Abstract】 Nephropathy Syndrome(NS) is a worldwide disease with a high incidence anddose harm to human physical and mental health. There are four clinical typesincluding a great deal of albuminuria, low albumen blood diease, high greasediease and apparent dropay. In the aspect of clinical therapy, hormone andimmunosuppressant including cortin, cell toxin, biological preparation are themost of the medicine commonly used in the western medicine to treat NS at theprecent. Due to the biggist toxin and side effect of incretion andimmunosuppressantrelatively looger using drug, and quite quabtitative suffers arenot sensitivity to the therapy. So exploring new approachs of treatment has manyimportant clinical values. Chinese traditional medicine has orginal departments inthe treatment of NS. At the present inside and outside of the country it had beenget the hightly attention. Empoldering and investigating new types of Chinesetraditional medicine to treat NS has become the hotapot in our research. Tongmai Granule (TM), is used as an effective Chinese traditional medicineclinically in the hospital belong to the Guangzhou University of Chinese traditionalmedicine. In order to provide the experimental basis for the clinical using, we havestudied the suppressive effect of TM on the model induced by puromycin aminonucleoside(PAN). In the part of paper, we expatiated on the knowledge of the name, pathogeny,pathogenesis, treatment, prescription of NS in the literatures of ancient Chinesetraditional medicine, and correlative knowledge of modern medicine. Then we carried out the following experiments: 1. Establishing PAN-treatedmodel. 2. The preventive effects of Tong-mai Granule on the model induced byPAN were evaluated. Sixty rats were divided into six groups. They are normalcontrol group、PAN-model group、Tong-mai Granule group of high, middle, lowdosage, ACE group, Urine samples were collected from the rats in metabolic cageson days 5, 10, 15, 20, 25 and 30 after the injection of PAN. All rats were sacrificed31 days after the injection of PAN for blood biochemistry, RNA preparation, lightmicroscopy and electrical microscopy of the kidneys. 3 、 We assayed theexperission of Bone morphogenetic protein(BMPs) and intracellular protein-Smadin the kidney. Our study indicates that we make the PAN-model successfully.The results ofthirty day’s observation showed that Tong-mai Granule could decrease urinaryprotein excretion, regulate abnormal blood fat metabolism, save renal function andimprove pathological changes in PAN model rats, inhibit of expression of BMPRIIand Smad1mRNA in the kidneys.更多还原