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诱导型一氧化氮合酶对内毒素休克小肠微循环的影响

师恩祎, 江晓菁, 白菡, 谷天祥, 中岛芳树

中国医科大学附属第一医院心脏外科.辽宁，沈阳 110004；中国医科大学附属第一医院麻醉科.辽宁，沈阳 110004；中国医科大学附属第二医院感染科.辽宁，沈阳 110004；日本浜松医科大学麻醉学系

摘要

采用静脉注射脂多糖（lipopolysaccharide, LPS）的方法建立小鼠内毒素休克模型，探讨内毒素休克时小肠微循环的变化以及诱导型一氧化氮合酶（iNOS）对小肠微循环的影响。实验过程中连续监测小鼠平均动脉血压(mean arterial pressure, MAP) 变化情况。利用FITC标记红细胞和活体显微镜方法直接观测并计算小鼠小肠绒毛尖端小动脉和毛细血管内红细胞的流速和流量，并观察敲除小鼠iNOS基因和选择性iNOS抑制剂S-methylthiourea sulfate (SMT)对实验过程中小肠微循环的影响。结果显示，对于野生型小鼠，应用SMT处理和敲除iNOS基因对基线的MAP、小肠绒毛尖端小动脉和毛细血管的红细胞流速和流量没有显著性差别。给予LPS后，小鼠的MAP进行性下降，给予LPS前，应用SMT和敲除小鼠iNOS基因可以显著提高MAP；给予LPS后，小鼠小肠绒毛尖端小动脉和毛细血管内红细胞流速和流量显著下降。给予LPS前，应用SMT和敲除小鼠iNOS基因可以显著提高小肠绒毛尖端小动脉和毛细血管的红细胞流速和流量。结果表明，iNOS在内毒素休克小肠微循环衰竭的过程中发挥重要作用。

关键词： 一氧化氮合酶; 内毒素休克; 微循环

Effect of inducible nitric oxide synthase on intestinal microcirculation in endotoxic shock

Shi Enwei, Jiang Xiaojing, Bai Han, Gu Tianxiang, Nakajima Yoshiki

Department of Cardiac Surgery, the First Affiliated Hospital, China Medical University.Shenyang 110001,Liaoning；China；Department of Infectious Disease,the Second Affiliated Hospital, China Medical University.Shenyang 110004,Liaoning

Abstract

To investigate the changes of intestinal microcirculation in endotoxic shock and the effect of inducible nitric oxide synthase (iNOS) on intestinal microcirculation, endotoxic shock was induced by intravenous injection of lipopolysaccharide (LPS) in mice. Mean arterial pressure (MAP) was monitored throughout the experimental procedure. The velocity and flux of red blood cell (RBC) in villus tip arteriole and capillaries were measured by FITC-labeled erythrocytes and intravital microscopy. The effect of iNOS was determined by targeted disruption of mice iNOS-gene and administration of S-methylthiourea sulfate (SMT), a selective inhibitor of iNOS, before LPS injection. No significant differences in MAP, RBC velocity and flux at baseline were found among wild type mice, SMT pretreated mice and iNOS-gene knockout mice. LPS induced a dramatic fall of MAP in wild type mice. The decrease of MAP was significantly restored in iNOS-gene knockout mice and in wild type mice received SMT before LPS injection. The velocity and flux of RBC in villus tip arteriole and capillaries decreased markedly after LPS injection in wild type mice, while significantly higher velocity and flux of RBC were found in iNOS-gene knockout mice and SMT-pretreated mice both 60 and 120 minutes after LPS injection. The results demonstrate that iNOS plays an essential role in the intestinal microcirculation disturbance which occurs in endotoxic shock.

Key words: Nitric oxide synthase;Endotoxic shock;Microcirculation

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引用本文：

师恩祎, 江晓菁, 白菡, 谷天祥, 中岛芳树. 诱导型一氧化氮合酶对内毒素休克小肠微循环的影响[J]. 生理学报 2005; 57 (1): .

Shi Enwei, Jiang Xiaojing, Bai Han, Gu Tianxiang, Nakajima Yoshiki. Effect of inducible nitric oxide synthase on intestinal microcirculation in endotoxic shock . Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).