【摘要】：目的：已有的研究提示青藤堿可以抑制模式識(shí)別受體的下游信號(hào)分子表達(dá)和信號(hào)轉(zhuǎn)導(dǎo),但其機(jī)理尚無(wú)深入的研究。本課題提出了青藤堿通過(guò)影響模式識(shí)別受體治療類風(fēng)濕關(guān)節(jié)炎的假說(shuō),通過(guò)在RA動(dòng)物模型器官組織和炎癥介質(zhì)水平上的研究,探索青藤堿對(duì)模式識(shí)別受體的影響與治療RA的相關(guān)性,為青藤堿的上市后再評(píng)價(jià)提供實(shí)驗(yàn)室依據(jù)。 方法：雄性SD大鼠50只,隨機(jī)分為5組,建立Ⅱ型膠原免疫大鼠誘導(dǎo)的關(guān)節(jié)炎模型(CIA)。以青藤堿高、中、低治療組與空白組、模型組作對(duì)照,定期測(cè)量大鼠體重和大鼠踝關(guān)節(jié)腫脹度,對(duì)大鼠踝關(guān)節(jié)滑膜組織作病理形態(tài)學(xué)觀察(HE染色),并取各組大鼠的關(guān)節(jié)滑膜組織,檢測(cè)TLR-2、NF-κB及相關(guān)細(xì)胞因子(TNF-α、IL-1)的表達(dá)率,運(yùn)用SPSS軟件進(jìn)行統(tǒng)計(jì)分析。 結(jié)果：1、類風(fēng)濕關(guān)節(jié)炎大鼠模型體重增長(zhǎng)速度減慢,青藤堿能夠有效抑制這種現(xiàn)象：2、青藤堿能夠有效的減輕大鼠踝關(guān)節(jié)的腫脹；3、青藤堿能夠降低大鼠TLR-2的表達(dá)水平,抑制大鼠關(guān)節(jié)滑膜炎癥相關(guān)指標(biāo)NF-κB、TNF-α、IL-1的表達(dá),抑制關(guān)節(jié)滑膜損傷、關(guān)節(jié)骨的破壞：4、隨著給藥劑量的增加,腫脹度越低,滑膜損傷和骨破壞越輕微,相關(guān)指標(biāo)的表達(dá)量也隨之降低：5、高劑量青藤堿組與中、低劑量組比較大鼠體重有所下降。 結(jié)論：青藤堿通過(guò)抑制APC細(xì)胞的模式識(shí)別受體TLR-2的表達(dá),抑制下游NF-κB的激活,使NF-κB信號(hào)通道的傳導(dǎo)受到抑制,阻斷APC的活化,使IL-1、INF-α等細(xì)胞因子的生成和分泌減少,抑制滑膜細(xì)胞的活化,使炎癥反應(yīng)和骨破壞得到抑制和延緩,從而達(dá)到抗類風(fēng)濕關(guān)節(jié)炎的作用。
[Abstract]:Aim: Sinomenine can inhibit the downstream signal expression and signal transduction of pattern recognition receptor, but its mechanism has not been further studied. In this study, the hypothesis of sinomenine in the treatment of rheumatoid arthritis through the influence pattern recognition receptor was put forward, which was studied at the level of organ tissue and inflammatory mediators in RA animal model. To explore the relationship between the effect of sinomenine on pattern recognition receptor and the treatment of RA, and to provide the laboratory basis for the post-marketing evaluation of sinomenine. Methods: fifty male SD rats were randomly divided into 5 groups to establish the type 鈪，

本文編號(hào)：2259560