基于TLR2－NF-κB信号转导研究黄芩苷抗类风湿关节炎的分子机制

RA的主要病理特点是病变关节滑膜过度增生和分泌促炎细胞因子。目前的抗RA药不利于RA的控制，故研制有效、低毒的抗RA药势在必行。临床治疗RA的许多复方药中含有黄芩,而黄芩的主要有效成分是黄芩苷。我们前期研究发现黄芩苷毒性很低，可显著增强RA患者滑膜成纤维细胞（RASFs）表达H3K4甲基化转移酶－ASH1L且抑制IL-6的分泌。有报道ASH1L可阻止炎症性自身免疫病的发生发展，由此推断黄芩苷可能通过上调RA滑膜ASH1L的基因表达、负调控TLR2－Myd88介导的NF-κB信号转导，进而抑制炎性细胞因子的分泌；建立RA动物模型，经黄芩苷干预治疗后，通过分析病变关节的病理改善程度评价药效；采用分子生物学方法从体内(RA动物)及体外(RASFs)两方面验证黄芩苷对ASH1L、H3K4甲基化及TLR2－Myd88介导的NF-κB转导途径关键分子的影响，探寻黄芩苷对RA的作用及其抗炎分子机制。

The main pathological characteristics of Rheumatoid arthritis (RA) is the excessive proliferation and secretion of inflammatory cytokines . Due to the current medicine for RA is not conducive to the RA control, so it is imperative to develop the effective, lowly toxic medicine for RA. Many of the traditional Chinese medicine in the clinical treatment for RA contains radix scutellariae, and its main effective components is baicalin. Our initial experiments found that baicalin has very low toxicity and can significantly increase the expression of H3K4 methylation transferase ASH1L and inhibit the secretion of IL-6 . According to RA synovial fibroblasts (RASFs) reports, ASH1L can prevent the occurrence of inflammatory autoimmune disease development.We infer that baicalin may incease the ASH1L expression in RA synovial membrane by negative regulatig of TLR2 -Myd88 mediated the NF-kB signaling, thus reducing the secretion of inflammatory cytokines; To prepair animal models of RA, and after the baicalin intervention, evaluate effect of medicine by analysing the pathological degree of improvement of joint ; Molecular biology methods were used on animals (RA) in vivo and in vitro (RASFs) to verify the effects of baicalin on key molecules of ASH1L, H3K4 methylation and TLR2 -Myd88 mediated the NF-kB pathway .This subjects was done to test the therapeutic effect of baicalin on RA and its anti-inflammatory molecular mechanisms.