肿瘤坏死因子α增强主动脉环收缩在感染性休克中的机制研究  

Mechanism Study on Strengthening Effect of Tumor Necrosis Factor-α on Aorta Ring Contraction Function in Septic Shock

作　　者：周莹[1] 刘沛[1] 

机构地区：[1]中国医科大学附属第一医院传染科,辽宁省沈阳市110001

出　　处：《中国全科医学》2014年第21期2457-2461,共5页Chinese General Practice

摘　　要：目的探讨肿瘤坏死因子α(TNF-α)对去内皮主动脉环反应性及主动脉血管平滑肌细胞(VSMC)内游离钙离子浓度([Ca2+]i)的影响,以证明TNF-α通过1,4,5-三磷酸肌醇受体(IP3Rs)增强VSMC对缩血管物质反应性是感染性休克早期维持血压稳定的重要机制。方法选取雄性Wistar大鼠24只制备离体去内皮主动脉环,随机分为去内皮对照组、去内皮TNF-α组、去内皮无钙对照组和去内皮无钙TNF-α组,各6只,给予血管紧张素Ⅱ(AngⅡ)刺激观察主动脉环收缩幅度。另选取3只Wistar大鼠分离鉴定原代VSMC,分为对照组和TNF-α组;另设上述2组于加AngⅡ前10 min加入IP3Rs阻断剂2-氨基乙氧基联苯硼酸盐(2-APB),即2-APB拮抗对照组和2-APB拮抗TNF-α组,观察在AngⅡ刺激后VSMC内[Ca2+]i的变化及阻断情况。结果有钙条件下,去内皮TNF-α组给予AngⅡ后主动脉环的收缩幅度高于去内皮对照组(P<0.05);无钙条件下,去内皮无钙TNF-α组给予AngⅡ后主动脉环的收缩幅度亦高于去内皮无钙对照组(P<0.05)。AngⅡ刺激可使VSMC内[Ca2+]i在短时间内迅速增加,TNF-α组[Ca2+]i升高值高于对照组、2-APB拮抗对照组和2-APB拮抗TNF-α组〔(1 315.1±496.4)与(411.6±80.3)、(13.1±9.8)、(18.7±11.9),P<0.05〕;而2-APB拮抗对照组、2-APB拮抗TNF-α组对AngⅡ刺激均失去反应,两组VSMC内[Ca2+]i间无差异(P>0.05)。结论 TNF-α可增加AngⅡ刺激VSMC引起的[Ca2+]i上升,进而引起去内皮主动脉环对AngⅡ反应性增强;证明TNF-α是通过IP3Rs通路产生效应的,这可能是感染性休克早期机体维持血压稳定的机制之一。ObjectiveTo investigatetheeffectoftumornecrosisfactor-α（TNF-α）onintracellularconcentration of free calciumion （ [ Ca2＋] i） of vascular smooth muscle cell （ VSMC） and reactiveness of aorta ring without endothelium , thus strengthening effect of TNF-αon VSMC′s responsiveness to vaso -excitor material through inositol 1, 4, 5-trisphophate recep-tors （ IP3 Rs） can be proved to be an important mechanism for maintaining stability of blood pressure in early stage of septic shock.Methods The in vitro aorta ring without endothelium came from 24 male Wistar rats, in vitro aorta rings without endothe-lium were divided into control group , TNF-αgroup, Ca2＋free control group , Ca2＋free TNF-αgroup, 6 cases in each group, the extent of aorta ring contraction induced by AngⅡwas detected.Primarily cultured VSMC from 3 Wistar rats were di-vided into TNF-αgroup and control group , and another two groups （2-APB antagonism control group and 2-APB antagonism TNF-αgroup） were treated with IP3 Rs blocker （2-APB） 10 min before adding AngⅡ, concentration changes and blocking -up of VSMC intracellular [ Ca2＋] I induced by AngⅡwere observed.Results After treatment with AngⅡunder Ca 2＋-present condition, the extent of aorta ring contraction in TNF-αgroup was significantly higher than that in control group （P〈0.05）. After treatment with AngⅡunder Ca 2＋-free condition , the extent of aorta ring contraction in Ca 2＋free TNF-αgroup was sig-nificantly higher than that in Ca 2＋free control group （ P〈0.05） .The VSMC intracellular [ Ca2＋] I increased rapidly by AngⅡ stimulation, [Ca2＋]I in TNF-αgroup （1 315.1 ±496.4） was significantly higher than that in control group , 2-APB antago-nism control group and 2-APB antagonism TNF-αgroup 〔 （411.6 ±80.3）, （13.1 ±9.8）, （18.7 ±11.9）〕 （P〈0.05）. 2-APB antagonism control group and 2-APB antagonism TNF-αgroup did not respond to AngⅡ stimulation, there was no significant difference in VSMC intracellu

关 键 词：休克 脓毒性 去内皮主动脉环 肌细胞 平滑肌 肿瘤坏死因子Α 血管紧张素Ⅱ 1 4 5-三磷酸肌醇受体 ANGIOTENSIN Ⅱ 

分 类 号：R631.4[医药卫生—外科学]