选择性阻断环鸟苷酸依赖性蛋白激酶Ⅰ对盲肠结扎穿孔致脓毒症大鼠血管环收缩功能的影响  

Effects of selective blockade of cyclic guanosine monophosphate-dependent protein kinase Ⅰ on contractility of vascular rings in rat model of cecal ligation and puncture-induced sepsis

作　　者：王海燕[1] 郭君[1] 王学敏[1] 

机构地区：[1]上海交通大学附属第六人民医院麻醉科,200233

出　　处：《上海医学》2012年第6期509-513,共5页Shanghai Medical Journal

摘　　要：目的探讨选择性阻断环鸟苷酸依赖性蛋白激酶Ⅰ(PKG-Ⅰ)对脓毒性休克大鼠血管低反应性的影响。方法将雄性Sprague-Dawley大鼠随机分为假手术组(SHAM组)、模型组(CLP组)、一氧化氮合成酶抑制剂组(L-NAME组)和PKG-Ⅰ特异性抑制剂组(DT-2组),每组20只。采用盲肠结扎穿孔法建立脓毒症模型,每组分别于造模后2、4、6h各取5只大鼠,分离胸主动脉制成血管环,L-NAME组和DT-2组血管在检测前分别与L-NAME或DT-2孵育30min。观测血管环对苯肾上腺素(PE)的浓度梯度效应曲线、最大收缩力(Emax)及产生Emax的半数有效浓度(EC50)。于造模后4h,每组各另取5只大鼠分离胸主动脉,采用光谱法定量检测其PKG-Ⅰ活性。结果造模后2、4、6h,CLP组的血管环收缩功能均显著低于SHAM组和L-NAME组(P值分别<0.05、0.01);造模后6h,L-NAME组显著低于SHAM组(P<0.05);造模后4h,DT-2组显著高于CLP组(P<0.05)。与SHAM组比较,CLP组造模后2、4、6h的Emax值均显著降低,但EC50值均显著升高(P值分别<0.05、0.01)。与CLP组比较,L-NAME组造模后2、4、6h的Emax值均显著升高,EC50均显著降低(P值分别<0.05、0.01)。DT-2组造模后4h的Emax值较CLP组显著升高,EC50显著降低(P值分别<0.05、0.01)。造模后4h,CLP组的PKG-Ⅰ活性值(0.905)较SHAM组(0.640)显著升高(P<0.01),L-NAME组及DT-2组的PKG-Ⅰ活性值(0.672、0.724)均较CLP组显著降低(P值均<0.05)。结论选择性阻断PKG-Ⅰ可部分恢复脓毒症大鼠血管环低反应性。Objective To investigate the effects of selective blockade of cyclic guanosine monophosphate （cGMP）-dependent protein kinase Ⅰ （PKG-Ⅰ ）on vascular hyporesponsiveness in septic shock rats, Methods Male Sprague-Dawley rats were randomly divided into sham operation （SHAM） group, cecal ligation and puncture （CLP） group, NG-nitro-L-arginine methylester （L-NAME） group andDT-2 trifluoroacetate salt （DT-2） group. There were 20 rats in each group. Septic shock was induced by CLP. Five rats were sacrificed in each group 2, 4 and 6 h after CLP, respectively. Thoracic aortas were prepared to measure the contraction-response curve, maximal tension （Emax） and medium effective concentration of Emax （EC50） to phenylephrine （PE）. The aortic rings were incubated with L-NAME （L-NAME group） or DT-2 （DT-2 group） for 30 mins before the measurement, At 4 h post- CLP, another 5 rats were used to quantitatively detect the activity of PKG- Ⅰ of aortic rings by spectrogscopy in each group. Results The contractibility of thoracic aortic rings of CLP group was significantly lower than those of SHAM group and L-NAME group 2,4 and 6 h after CLP （P〈0.05 or 0.01）. But the contractibility of aortic rings from L-NAME group was significantly lower than that from SHAM group 6 h after CLP （P〈 0. 05）, and the contractibility in DT-2 group was significantly higher than CLP group 4 h after CLP （P〈0. 05）. At 2, 4 and 6 h post-CLP, compared with SHAM group the Emax was significantly decreased and EO50 was significantly increasedin CLP group （P〈0.05 or 0.01）. Compared with CLP group, Emax was significantly increased and EC50 was significantly decreased in L-NAME group （P〈0.05 or 0.01）. Emax of DT-2 group was significantly higher and EC50 was significantly lower than those of CLP group 4 h after CLP （P〈0.05 or 0.01）. At 4 h post-OLP, the activity of PKG- Ⅰ in CLP group was significantly higher than that in SHAM group （0. 905 vs. 0. 640, P〈0.01 ） ; the activities in

关 键 词：脓毒症 血管低反应性 血管环 环鸟苷酸依赖性蛋白激酶 

分 类 号：R459.7[医药卫生—急诊医学]