IL-1β下调Rho激酶活性介导脓毒症大鼠血管钙失敏的机制研究

发布时间：2018-01-13 01:16

本文关键词：IL-1β下调Rho激酶活性介导脓毒症大鼠血管钙失敏的机制研究　出处：《重庆医学》2017年28期 　论文类型：期刊论文

【摘要】：目的探讨白细胞介素(IL)-1β下调Rho激酶活性介导脓毒症大鼠血管钙失敏的机制。方法 SD大鼠32只,按随机数字表完全随机分为假手术组、盲肠结扎穿孔(CLP)3h组、CLP 6h组、CLP 12h组,每组8只。经CLP复制脓毒症大鼠模型,检测不同时点血浆IL-1β浓度及肠系膜上动脉(SMAs)钙敏感性,分析二者之间的相关性。培养SMAs来源的血管平滑肌细胞(VSMCs)并与不同浓度重组人IL-1β孵育24h,观察IL-1β对其肌球蛋白轻链(MLC20)磷酸化水平、Rho激酶活性、G蛋白表达水平及RhoGEFs活性的影响。结果经CLP 3h后SMAs钙敏感性开始下降(P0.05),而血浆IL-1β在CLP 6h后开始上升(P0.05),SMAs钙敏感性变化趋势与血浆IL-1β浓度变化呈明显负相关(P0.05)。IL-1β可降低VSMCs MLC_(20)磷酸化水平及Rho激酶活性(P0.05),上调Gα11表达而下调Gα12表达(P0.05),但对Gαq和Gα13表达无明显作用(P0.05)。IL-1β可明显降低RhoGEF和PDZ-RhoGEF活性(P0.05),升高p63RhoGEF活性(P0.05)。结论 IL-1β通过下调Gα12表达,引起PDZ-RhoGEF和Rho激酶的活性下降,导致MLC_(20)磷酸化水平下降从而介导脓毒症大鼠血管钙失敏的发生;另外也能通过上调Gα11表达,引起p63RhoGEF活性增加而介导脓毒症大鼠血管钙敏感性增加,但总效应是使钙敏感性降低。
[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 伪 11 was up-regulated and the expression of G 伪 12 was down-regulated (P 0.05). However, the expression of G 伪 Q and G 伪 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 伪 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 伪 11 expression, which mediated the increase of vascular calcium sensitivity in septic rats, but the total effect was to decrease calcium sensitivity.
【作者单位】：空军杭州航空医学鉴定训练中心医学疗养部;第三军医大学大坪医院野战外科研究所二室/创伤烧伤与复合伤国家重点实验室;
【基金】：国家杰出青年科学基金资助项目(30625037)
【分类号】：R459.7
【正文快照】： 脓毒症、脓毒性休克是重症监护室最常见的并发症之一,尽管对其研究投入了大量的人力、物力,但其病死率始终居高不下[1]。血管低反应性(即血管对血管活性药物的反应性下降甚至不反应)是导致其高病死率的重要原因[2]。目前认为血管低反应性的发生机制主要有:(1)受体失敏,血管舒

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