IL-1β介导脓毒症大鼠血管α1肾上腺素能受体失敏机制的研究  

Study on mechanism of interleukin-1β for mediating vascular α1 adrenergic receptors desensitization in septic rats

作　　者：梁家林 刘良明[2] 董惠 LIANG Jialin;LIU Liangming;DONG Hui(Hangzhou Rehabilitative Center for Special Services of Air Force, Hangzhou, Zhejiang 310013, China;Department 2, Institute of Field Surgery Research/State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital of Army Military Medical University,Chongqing 400042,China;Institute of Immunology Research,Army Medical University,Chongqing 400038, China)

机构地区：[1]空军杭州特勤疗养中心,杭州,310013 [2]陆军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,重庆,400042 [3]陆军军医大学免疫研究所,重庆,400038

出　　处：《重庆医学》2019年第13期2167-2170,2174,共5页Chongqing medicine

基　　金：国家杰出青年科学基金项目(30625037)

摘　　要：目的探讨白细胞介素(IL)-1β介导脓毒症大鼠血管α1肾上腺素能受体(α1ARs)失敏的机制。方法经盲肠结扎穿孔(CLP)复制脓毒症大鼠模型,检测假手术组,CLP后3、6、12h肠系膜上动脉(SMAs)α1ARs敏感性及蛋白表达,分析其与血浆IL-1β水平的关系。采用重组大鼠IL-1β孵育大鼠血管平滑肌细胞(VSMCs),观察IL-1β对α1ARs的蛋白表达、mRNA稳定性、启动子活性,以及AP2、Sp1蛋白表达的影响。运用RNAi技术,观察Sp1和AP2siRNA对VSMCs α1ARs蛋白表达的影响。结果 CLP 3h后SMAs α1ARs敏感性及蛋白表达即明显下降(P<0.05),与血浆IL-1β水平变化呈明显负相关(P<0.05)。IL-1β可降低VSMCs α1ARs、AP2、Sp1蛋白表达(P<0.05)、α1DAR启动子活性(P<0.05),但不改变α1ARs mRNA的稳定性(P>0.05)。Sp1和AP2siRNA均降低VSMCs的α1ARs蛋白表达(P<0.05)。结论 IL-1β通过下调转录因子Sp1、AP2表达,在转录而不是转录后水平下调α1ARs表达,介导脓毒症血管α1ARs失敏的发生。Objective To investigate the mechanism of interleukin-1β(IL-1β)for mediating the vascular α1 adrenergic receptors(α1ARs)desensitization in septic rats.Methods The septic rat model was duplicated by cecal ligation and puncture(CLP).Then the α1ARs sensitivity and protein expression of rat superior mesenteric arteries(SMAs)at 3,6,12 hafter CLP in the sham operation group were measured,and their relationship with plasma IL-1β level was analyzed.Vascular smooth muscle cells(VSMCs)derived from SMAs of rats were incubated with IL-1β.Then its influences on the protein expression,mRNA stability and promoter activity of α1ARs,AP2 and Sp1 protein expression were observed.The influence of Sp1 and AP2 siRNA on α1ARs protein expression of VSMCs was observed using RNAi technology.Results The α1ARs sensitivity and protein expression of rat SMAs since 3 hafter CLP were significantly reduced(P<0.05),which were negatively correlate with plasma IL-1β level change(P<0.05).The α1ARs protein expression,activity of α1DAR promoter,AP2 and Sp1 protein expression were all significantly reduced by IL-1β(P<0.05),while the mRNA stability of α1ARs was not changed(P>0.05).The α1ARs protein expression of VSMCs decreased by Sp1 and AP2 siRNA(P<0.05).Conclusion IL-1β down-regulates the α1ARs expression in the transcriptional level rather than post-transcriptional level through down-regulating the expression of transcriptional factors Sp1 and AP2,and mediates the septic vascular α1ARs desensitization occurrence.

关 键 词：脓毒症 白细胞介素1Β 受体 肾上腺素能α1 SP1 AP2 

分 类 号：R543.7[医药卫生—心血管疾病]