本文關(guān)鍵詞：IL-1β下調(diào)Rho激酶活性介導(dǎo)膿毒癥大鼠血管鈣失敏的機制研究　出處：《重慶醫(yī)學(xué)》2017年28期 　論文類型：期刊論文

  更多相關(guān)文章： 膿毒癥 白細胞介素β 鈣失敏 G蛋白 RhoGEF

【摘要】：目的探討白細胞介素(IL)-1β下調(diào)Rho激酶活性介導(dǎo)膿毒癥大鼠血管鈣失敏的機制。方法 SD大鼠32只,按隨機數(shù)字表完全隨機分為假手術(shù)組、盲腸結(jié)扎穿孔(CLP)3h組、CLP 6h組、CLP 12h組,每組8只。經(jīng)CLP復(fù)制膿毒癥大鼠模型,檢測不同時點血漿IL-1β濃度及腸系膜上動脈(SMAs)鈣敏感性,分析二者之間的相關(guān)性。培養(yǎng)SMAs來源的血管平滑肌細胞(VSMCs)并與不同濃度重組人IL-1β孵育24h,觀察IL-1β對其肌球蛋白輕鏈(MLC20)磷酸化水平、Rho激酶活性、G蛋白表達水平及RhoGEFs活性的影響。結(jié)果經(jīng)CLP 3h后SMAs鈣敏感性開始下降(P0.05),而血漿IL-1β在CLP 6h后開始上升(P0.05),SMAs鈣敏感性變化趨勢與血漿IL-1β濃度變化呈明顯負相關(guān)(P0.05)。IL-1β可降低VSMCs MLC_(20)磷酸化水平及Rho激酶活性(P0.05),上調(diào)Gα11表達而下調(diào)Gα12表達(P0.05),但對Gαq和Gα13表達無明顯作用(P0.05)。IL-1β可明顯降低RhoGEF和PDZ-RhoGEF活性(P0.05),升高p63RhoGEF活性(P0.05)。結(jié)論 IL-1β通過下調(diào)Gα12表達,引起PDZ-RhoGEF和Rho激酶的活性下降,導(dǎo)致MLC_(20)磷酸化水平下降從而介導(dǎo)膿毒癥大鼠血管鈣失敏的發(fā)生;另外也能通過上調(diào)Gα11表達,引起p63RhoGEF活性增加而介導(dǎo)膿毒癥大鼠血管鈣敏感性增加,但總效應(yīng)是使鈣敏感性降低。
[Abstract]:Objective to investigate the mechanism of interleukin-1 尾 down-regulation of Rho kinase activity mediated vascular calcium desensitization in septic rats. Methods Thirty-two SD rats were randomly divided into sham operation group according to random digital table. The sepsis rat model was induced by CLP in the cecal ligation and perforation group (n = 8). Plasma IL-1 尾 concentration and calcium sensitivity of superior mesenteric artery (SMA) were detected at different time points. Vascular smooth muscle cells derived from SMAs were cultured and incubated with different concentrations of recombinant human IL-1 尾 for 24 hours. The phosphorylation level of IL-1 尾 on myosin light chain (MLC20) was observed. Results after 3 hours of CLP, the calcium sensitivity of SMAs began to decrease (P 0.05). However, plasma IL-1 尾 began to rise after 6 hours of CLP (P 0.05). There was a significant negative correlation between the change of calcium sensitivity of SMAs and the change of plasma IL-1 尾 concentration. IL-1 尾 decreased VSMCs MLC tipping 20 (P < 0.05). Phosphorylation level and Rho kinase activity (P0.05). The expression of G 偽 11 was up-regulated and the expression of G 偽 12 was down-regulated (P 0.05). However, the expression of G 偽 Q and G 偽 13 had no significant effect on the expression of P0.05A. IL-1 尾 could significantly reduce the activities of RhoGEF and PDZ-RhoGEF (P0.05). Conclusion IL-1 尾 can decrease the activity of PDZ-RhoGEF and Rho kinase by down-regulating the expression of G 偽 12. The decrease of phosphorylation level of MLC + + 20) mediates the occurrence of vascular calcium desensitization in septic rats. In addition, p63 RhoGEF activity was increased by up-regulation of G 偽 11 expression, which mediated the increase of vascular calcium sensitivity in septic rats, but the total effect was to decrease calcium sensitivity.
【作者單位】： 空軍杭州航空醫(yī)學(xué)鑒定訓(xùn)練中心醫(yī)學(xué)療養(yǎng)部;第三軍醫(yī)大學(xué)大坪醫(yī)院野戰(zhàn)外科研究所二室/創(chuàng)傷燒傷與復(fù)合傷國家重點實驗室;
【基金】：國家杰出青年科學(xué)基金資助項目(30625037)
【分類號】：R459.7
【正文快照】： 膿毒癥、膿毒性休克是重癥監(jiān)護室最常見的并發(fā)癥之一,盡管對其研究投入了大量的人力、物力,但其病死率始終居高不下[1]。血管低反應(yīng)性(即血管對血管活性藥物的反應(yīng)性下降甚至不反應(yīng))是導(dǎo)致其高病死率的重要原因[2]。目前認為血管低反應(yīng)性的發(fā)生機制主要有:(1)受體失敏,血管舒

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