论文标题:补肾通络方治疗类风湿性关节炎的理论、临床和实验研究 Effect and Mechanism of Selenium-enriched Malt on Hepatocarcinogenesis Induced by Diethylnitrosamine in Rats 论文作者 宋红莉 论文导师 李兴广,论文学位 硕士,论文专业 临床中药学 论文单位 北京中医药大学,点击次数 1012,论文页数 97页File Size1370k 2005-05-01论文网 http://www.lw23.com/lunwen_176302/ 补肾通络; 类风湿关节炎; 佐剂性关节炎 AA model;immunosuppression; Rheumatoid arthritis 1.理论研究 类风湿性关节炎(RA)是一种慢性炎症性疾病,是以对称性多关节炎病变为主要临床表现的全身性自身免疫性疾病。其特点是关节滑膜的慢性炎症、软骨吸收、骨质破坏和骨质纤维化。类风湿性关节炎在各年龄中均可发病,成人中多发于中年女性。本病为慢性、进行性、侵袭性疾病,如不给予适当的治疗,病情会逐步发展加重,造成对骨关节的破坏,最后导致关节强直、畸形、功能丧失。 类风湿性关节炎的发病机理目前尚未完全阐明,各国学者其发病机制进行了深入地研究,结果表明:类风湿关节炎患者下丘脑-垂体-肾上腺(HPA)轴功能存在一定程度的异常,有关 RA 病因及发病机制的研究证实,RA 患者 HPA轴功能下降,可能是滑膜炎症产生和持续存在的重要因素。HPA 轴是通过其分泌的糖皮质激素抑制免疫细胞释放细胞因子,减轻淋巴细胞浸润和迁移而达到抗炎的作用。 结合以往的文献研究与阎明华主任中医师的临床治疗经验,我们认为该病的病因是肾虚,尤以肾阳不足为发病的重要原因,肾阳不足,风寒湿邪乘虚侵袭,痹阻脉络,络道不通,发而为痹,且在病程中易挟痰挟瘀。通过对中医“肾本质”的研究,发现不同病种的肾虚患者 HPA 轴功能低下,并揭示温补肾阳方药是调节 HPA 轴的有效手段。因 RA 发病的重要内因为肾阳虚,而反应肾阳虚的一个重要的客观指标 17-羟类固醇(17-OHCS)和血清皮质醇,为HPA 轴的产物,故 RA 的治疗应从肾论治,以调整 HPA 轴功能为目的。 针对类风湿关节炎发病的病因病机,我们制定了温补肾阳,通络止痛的治疗方法来治疗类风湿关节炎。 2.临床研究 60 例 RA 患者随机分为两组,治疗组 30 例应用补肾通络方,对照组 30 例应用雷公藤多甙片,治疗 1 个月后观察临床疗效(晨僵、关节疼痛、肿胀及关节功能),观察治疗前后 ESR、CRP、RF、Ig、皮质醇的变化及不良反应。结果补肾通络方治疗 RA 的总有效率为 96.7%,并且在改善关节症状(晨僵、疼痛、肿胀、关节功能)及实验室指标方面(ESR、RF、CRP、IgA、IgG、IgM、皮质醇)均优于雷公藤多甙片组,两组相比差异均显著 P<0.05,且无明显的不良反应。 3.实验研究 3.1 实验一:大鼠肾阳虚痹证模型的制备。20 只大鼠,随机分为正常组和模型组。模型组给予完全弗氏佐剂制作关节炎模型(AA),并给予羟基脲灌胃制作肾阳虚模型,以两种因素制作肾阳虚型 AA 关节炎模型。观察各组大鼠的足跖肿胀度,测尿 17-OHCS 的变化。结果显示模型组大鼠的足肿胀明显,并且17-OHCS 下降明显,与正常组相比 P<0.05,说明肾阳虚 AA 大鼠模型制备成 1 Theory research: Rheumatoid arthritis(RA) is a common chronic inflammatory disorder involving the synovial membranes of multiple joints.Although rheumatoid arthritis is thought of an autoimmune disease,its aetiology is unknown.And it is probably the most common source of disability.It needs further exploration of these influences urgently because current therapies frequently fail to interrupt the established disease process. According to the theory of Tranditional Chinese Medicine(TCM),summing up TCM’s recognize on RA , advancing TCM’s pathological mechanism ,therapeutic principle and method. To sum up the tutor’s experience on the treatement of RA and draft the therapeutic method and prescription ─Bushentongluo fang(BSF) on RA based on “kidney”. TCM’s pathotogic mechanism of RA was deficiency of the kidney.Kidney deficiency played an important role in the invasion of RA,and kidney deficiency has close contact with the Hypothalamus-Pituitary-Adrenal(HPA) axis,and HPA axis has close contact with RA,so we can suppose that supplying kidney can adjust the HPA axis ,and therapy RA. 2 Clinical research 60 cases of RA were divided into two groups.The treatment group(n=30) was treated with BSF.The control group (n=30)was treated with tripterygium wilfoudii polycoside tablet(TPT).Two groups were treated for one course all.The results of clinical research:The effect of BSF was similar to TPT in the total effective rate,improving the joint symptoms et al.But the BSF was superior to TPT in improving general symptoms of the patients with RA,regulating the balance of HPA axis. 3 Experimental research Animal models of RA especially adjuvant arthritis(AA) in rats has much character similar to human RA in pathological mechanism ,clinical representation and so on. The model is more ideal in investigating RA and selecting drugs of anti-inflammation and immunity.To discuss the pathological mechanism and the relation between animal models of RA and clinic will be important not only to research RA in pathology,physiology,nervous-endocrine-immunity and so on, but also to find out safety and effective drugs of treatment RA. TCM’s pathotogic mechanism of RA was deficiency of the kidney,so we use Hydroxy-carbamide Tablets to make the model of kidney deficiency of yang-qi.So we have the model of kidney deficiency in AA. The results of experimental research:The swelling degree of posterior metatarsus in BSF and TPT group obviously lowered after treatment.The arthritis index (AI)of BSF and TPT treated group was markedly decreased after treatment,and the 12g/kg group is more obviously than the 4g/kg group.The increment of rat body weight in BSF treated group wasn’t significantly different from that of normal control group,but was significantly different from that of model control group.The 17-OHCS and Cort of the 12 g/kg BSF group were higher than the 4g/kg BSF group and the TPT group.The BSF group can restraining the inflammation and the hyperplasia of synovial membranes. 4 In conclusion,the results indicated that BSF could take a good effect in the treatment of RA,from the thought of supply kidney and adjust the HPA axis.The research also accomplish the exploration on the theoretical study and animal experiment based on the TCM theory. It suggests that in regulating on the endocrine system by the TCM herbs can improve the immune system and reduce the damage of RA ,and it is a useful method to treat the RA in the future.
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