藏药浴的文化内涵及五味甘露药浴颗粒对AA模型大鼠滑膜细胞的炎症信号通路调控机制研究

发布时间：2018-06-06 06:02

本文选题：藏药浴 + 文化内涵　；参考：《成都中医药大学》2016年硕士论文

【摘要】：类风湿性关节炎(RA)——属于藏医“真布病”范畴,在藏区是一种常见疑难性疾病,其发病率高,致残率高,并可累及多器官、多系统引起系统性疾病。藏药浴疗法是藏医对RA临床效果确切的常用手段,而“五味甘露”药浴是藏医临床上治疗RA主要使用的成方制剂。藏药浴已经成为国家非物质文化遗产保护项目,以及国家中医药管理局藏医重点专科。目前,对藏药浴“五味甘露”的研究主要集中在临床疗效与浴后护理方面,藏药浴对调整机体免疫系统的显效性和高治愈率的研究也比较广泛。但从细胞层面对藏药五味甘露药浴颗粒作用于机体的机制缺乏系统科学的研究,对其抗RA的分子作用机制的研究尚不深入。目的：从藏医学理论及藏药浴文化内涵入手,以藏药浴临床经验为指导,开展藏药五味甘露药浴颗粒药效及其作用机制实验研究。从整体动物模型层面,考察五味甘露药颗粒在治疗RA大鼠关节炎症上的药效作用；从细胞层面,分析其对RA大鼠滑膜组织中细胞因子的影响以及对蛋白表达的调控作用；从分析生物学层面,筛选与RA相关的分子信息,探讨五味甘露药浴颗粒对RA滑膜细胞的JAK-STAT炎症信号通路调控机制。方法：1.文化研究：从医学人类学的视野,结合具体的藏医学历史和藏族沐浴文化背景,整合文献学、田野调查等研究方法来阐释藏药浴的文化内涵。2.实验研究：将大鼠造模经藏药浴治疗后：①采用致炎后足容积测量、免疫器官的脏器系数、及踝关节病理形态的比较,评价五味甘露药浴颗粒对AA大鼠的治疗效果；②采用酶联反应、免疫组化法检测并分析五味甘露药浴颗粒对滑膜组织中细胞因子及蛋白表达的干预效应；③采用基因芯片技术,检测滑膜细胞中的JAK-STAT信号通路中相关信号分子的表达,并用RT-PCR法进行验证,探讨五味甘露药浴颗粒对RA滑膜细胞的JAK-STAT信号通路的调控机制。结果：1.拥有一千多年历史的藏药浴蕴含着丰富的藏族沐浴文化,并以藏医药理论为指导在临床广泛开展。它集医疗、养生、保健等多种功能于一体,是具有历史、文化、经济等多重价值的藏医外治疗法。2.五味甘露药浴颗粒高剂量组(11.80 g·L-1)、中剂量组(5.90 g·L-1)低剂量组(2.95 g·-1)AA大鼠原发性足肿胀度均有减轻,滑膜细胞增生、炎细胞浸润、关节软骨破坏均有不同程度的改善；血清中白细胞介素-1p(IL-1β)肿瘤坏死因子-α (TNF-α)、生长因子(EGF、bFGF、PDGF-BB)、前列腺素E2 (PGE2)、基质金属蛋白酶(MMP-3、TIMP-1)的含量均有不同程度的下降。该药可以抑制滑膜细胞JAK-STAT信号通路的激活,使P-STAT1、P-STAT3、IL-6表达下降,IL-10表达上升；在JAK-STAT信号通路上I12rb、Mp1、Stam等相关信号分子表达上调,PIAS1、PIAS3、SOCS4、EPO、IFNGR2等相关信号分子表达下调。结论：1.藏药浴既是生物学意义上的科学,也是人类学意义上的文化,具有自然科学和人文科学的双重特征。要充分理解藏医药文化内涵,把人文文化和科学文化相融,借鉴西医的科学技术手段开展对藏药浴的现代研究。2.藏药浴(五味甘露药浴颗粒)在类风湿关节炎滑膜病理改变的过程中,通过下调致炎因子(TNF-α、IL-1,6)等、上调抗炎因子(IL-10)来激活体内免疫系统,抑制成纤维样滑膜细胞分泌各类细胞因子对滑膜的刺激,来控制关节滑膜炎症。对滑膜细胞JAK-STAT炎症信号通路中相关信号分子的表达有良性调节作用,进而调控细胞核内基因转录,而最终达到抑制RA滑膜细胞增殖、促进细胞凋亡、抗炎消肿、保护关节骨与软骨的目的。
[Abstract]:Rheumatoid arthritis (RA), which belongs to the category of "true cloth disease" of Tibetan medicine, is a common and difficult disease in Tibetan area. It has high incidence, high disability rate, and can involve multiple organs and multiple systems to cause systemic disease. Tibetan medicine bath therapy is the exact use of Tibetan Medicine to the clinical effect of RA. The "five flavour manna" medicine bath is the clinical treatment of Tibetan medicine. The Tibetan medicine bathing has become the national intangible cultural heritage protection project, and the national medicine administration bureau of the National Medicine Management Bureau of the national key specialist in Tibetan medicine. At present, the study of "five flavor manna" in the Tibetan medicine bath is mainly focused on the clinical efficacy and post bath nursing. The Tibetan medicine bath has a good effect on the adjustment of the immune system of the body and Gao Zhiyu, and Gao Zhiyu The research on the rate is also widespread. However, the mechanism of the five flavour manna medicine bath particles in the Tibetan medicine is lack of systematic scientific research. The research on the mechanism of its anti RA molecular action is still not thorough. Experimental study on the effect and mechanism of drug bathing granules. From the whole animal model level, the effect of five flavour manna particles on the arthritis of RA rats was investigated, and the effects on the cytokines in the synovial tissue and the regulation of protein expression in the synovial tissue of RA rats were analyzed from the cell level. With the molecular information related to RA, the regulation mechanism of the JAK-STAT inflammatory signaling pathway of five flavour manna medicine bath particles on RA synovial cells was discussed. Methods: 1. cultural studies: from the perspective of medical anthropology, combining specific Tibetan medical history and Tibetan bath culture background, integrating literature, field field investigation and other research methods to elucidate the culture of Tibetan medicine bath Intension.2. experimental study: after the treatment of rat model Tibetan medicine bath: (1) the effect of five flavour manna medicine bath particles on AA rats was evaluated by measuring the volume of post inflammatory foot volume, the organ coefficient of the immune organs, and the pathological morphology of the ankle joint. Secondly, the enzyme linked reaction and immunohistochemical method were used to detect and analyze the five flavored manna bathing granules. The interference effect of cytokine and protein expression in synovial tissue; (3) using gene chip technology to detect the expression of related signal molecules in the JAK-STAT signal pathway in synovial cells, and to verify the regulation mechanism of the JAK-STAT signaling pathway of five flavour manna drug bath particles on RA synovial cells by RT-PCR method. Tibetan medicine bath for more than a thousand years contains rich Tibetan bathing culture, and is widely carried out in clinical practice with the guidance of Tibetan medicine theory. It integrates medical, health, health and other functions. It is a high dose group of Tibetan medicine.2. five flavour manna medicine bath granules (11.80 G. L-1) with multiple values of history, culture and economy. 5.90 G. L-1) low dose group (2.95 G. -1) in AA rats, the primary foot swelling was reduced, synovial cell proliferation, inflammatory cell infiltration, and articular cartilage destruction were improved in varying degrees; serum interleukin -1p (IL-1 beta) tumor necrosis factor alpha (TNF- alpha), growth factor (EGF, bFGF, PDGF-BB), prostaglandin E2 (-1), matrix metalloproteinase The content of the enzyme (MMP-3, TIMP-1) decreased in varying degrees. The drug could inhibit the activation of the JAK-STAT signaling pathway in synovial cells, decrease the expression of P-STAT1, P-STAT3, IL-6, and increase the expression of IL-10, and the expression of I12rb, Mp1, Stam and other related signal molecules expressed in JAK-STAT signaling pathway. Conclusion: 1. the Tibetan medicine bath is both the science of biology and the culture in the sense of anthropology, which has the dual characteristics of natural science and humanities. It is necessary to fully understand the cultural connotation of Tibetan medicine, combine the humanities and scientific culture, and use the scientific and technological means of Western medicine to carry out the modern study of Tibetan medicine bath for Tibetan medicine bath (.2. Tibetan medicine bath). In the course of the pathological changes of rheumatoid arthritis synovial membrane, the anti inflammatory factor (IL-10) is up regulated by down regulation of inflammatory factors (TNF- alpha, IL-1,6) to activate the immune system in the process of rheumatoid arthritis, and inhibit the stimulation of synovial membrane by the secretion of various cytokines from fibroid synovial cells to control synovial inflammation of the synovial membrane. JAK-STAT of synovial cells. The expression of related signal molecules in the inflammatory signaling pathway has a benign regulation effect, and then regulates the gene transcription in the nucleus, and ultimately can inhibit the proliferation of RA synovial cells, promote cell apoptosis, anti inflammation and swelling, and protect the bone and cartilage of the joint.
【学位授予单位】：成都中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R29

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