本文關(guān)鍵詞： 激活素 受體相互作用蛋白 信號(hào)傳導(dǎo) 巨噬細(xì)胞 IL-1β NO RT-PCR Western blotting　出處：《吉林大學(xué)》2006年博士論文　論文類型：學(xué)位論文

【摘要】：激活素(Activin)屬于TGFβ超家族成員,在神經(jīng)細(xì)胞分化誘導(dǎo)、造血細(xì)胞增殖和分化、內(nèi)分泌中樞垂體性激素分泌調(diào)節(jié)等多方面發(fā)揮重要作用,同時(shí)激活素還是組織修復(fù)、再生和分化的重要調(diào)節(jié)因子,參與機(jī)體炎癥和急性期反應(yīng)。巨噬細(xì)胞是參與機(jī)體炎性應(yīng)答的主要細(xì)胞,前期研究發(fā)現(xiàn)激活素可以調(diào)控巨噬細(xì)胞分泌NO,其作用與巨噬細(xì)胞活化狀態(tài)有關(guān)。本研究進(jìn)一步探討激活素對(duì)巨噬細(xì)胞活性的調(diào)節(jié)作用及其可能的信號(hào)傳導(dǎo)機(jī)制。 巨噬細(xì)胞不僅具有分泌細(xì)胞因子、NO等作用,還是重要的吞噬細(xì)胞。因此,本研究采用原代培養(yǎng)C57BL/6小鼠腹腔巨噬細(xì)胞、傳代培養(yǎng)BALB/c小鼠巨噬細(xì)胞系RAW264.7細(xì)胞為實(shí)驗(yàn)對(duì)象,通過分析IL-1β、NO的分泌、IL-1β、iNOS mRNA表達(dá)及細(xì)胞吞噬活性,系統(tǒng)探討激活素A對(duì)巨噬細(xì)胞活性的雙向調(diào)控作用。實(shí)驗(yàn)表明,激活素A刺激小鼠巨噬細(xì)胞炎性因子產(chǎn)生、增強(qiáng)吞噬活性,具有劑量依賴關(guān)系;而對(duì)LPS活化小鼠巨噬細(xì)胞的活性具有明顯抑制作用。提示激活素對(duì)巨噬細(xì)胞的分泌活性和吞噬活性,均具有雙向調(diào)節(jié)作用,此作用與巨噬細(xì)胞的激活狀態(tài)有關(guān)。其作用有助于維持機(jī)體生理平衡,防止因炎癥反應(yīng)過度而造成的損害。 激活素對(duì)細(xì)胞的作用具有明顯的組織學(xué)特異性,其作用的特異性與其受體后信號(hào)傳導(dǎo)差異有關(guān),前期研究表明巨噬細(xì)胞高表達(dá)激活素Ⅱ型受體(ActRⅡA)。圍繞ActRⅡA信號(hào)傳導(dǎo)途徑的研究,發(fā)現(xiàn)了新的信號(hào)調(diào)控蛋白——激活素受體相互作用蛋白(ActRIP),為明確ActRIPs參與巨噬細(xì)胞活性調(diào)控的信號(hào)傳導(dǎo)機(jī)制。實(shí)驗(yàn)采用基因過表達(dá)技術(shù),將ActRIP2、3導(dǎo)入小鼠巨噬細(xì)胞,結(jié)果顯示,ActRIP2抑制小鼠巨噬細(xì)胞NO的分泌及iNOS、IL-1 mRNA表達(dá),而ActRIP3促進(jìn)NO的分泌及iNOS、IL-1 mRNA表達(dá)。激活素刺激小鼠巨噬細(xì)胞
[Abstract]:Activinin, a member of TGF 尾 superfamily, plays an important role in the induction of neuronal differentiation, proliferation and differentiation of hematopoietic cells, and regulation of pituitary hormone secretion in endocrine center. At the same time activin is also an important regulator of tissue repair regeneration and differentiation involved in inflammation and acute phase reaction. Macrophages are the main cells involved in the body inflammatory response. Previous studies have shown that activin can regulate the secretion of no by macrophages. The effect of activin on the activity of macrophages and its possible signal transduction mechanism were investigated. Macrophages not only secrete cytokines, such as no, but also important phagocytes. Therefore, the primary culture of C57BL / 6 mouse peritoneal macrophages was carried out in this study. BALB/c murine macrophage cell line RAW264.7 was subcultured and the secretion of IL-1 尾 no was analyzed. The expression of iNOS mRNA and the phagocytic activity of macrophages were studied systematically. The results showed that activin A stimulated the production of macrophage inflammatory factors in mice. The phagocytic activity was enhanced in a dose-dependent manner. The activity of macrophages activated by LPS was inhibited obviously, which indicated that activin had bidirectional regulation on the secretion activity and phagocytic activity of macrophages. This action is related to the activation of macrophages. It helps to maintain the physiological balance of the body and prevent the damage caused by excessive inflammatory reaction. The effect of activin on cells is histologically specific, and its specificity is related to the difference of signal transduction after receptor. Previous studies have shown that macrophages overexpression activin type 鈪，

本文編號(hào)：1480489