CAJ | 학술논문

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察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.
채용정맥주사지다당(lipopolysaccharide,LPS)적방법건립소서내독소휴극모형,탐토내독소휴극시소장미순배적변화이급유도형일양화담합매(iNOS)대소장미순배적영향.실험과정중련속감측소서평균동맥혈압(mean arterial pressure,MAP)변화정황.이용FITC표기홍세포화활체현미경방법직접관찰병계산소서소장융모첨단소동맥화모세혈관내홍세포적류속화류량,병관찰고제소서iNOS기인화선택성iNOS억제제S-methylthiourea sulfate(SMT)대실험과정중소장미순배적영향.결과현시,대우야생형소서,응용SMT처리화고제iNOS기인대기선적MAP、소장융모첨단소동맥화모세혈관적홍세포류속화류량몰유현저성차별.급여LPS후,소서적MAP진행성하강.급여LPS전,응용SMT화고제소서iNOS기인가이현저제고MAP;급여LPS후,소서소장융모첨단소동맥화모세혈관내홍세포류속화류량현저하강.급여LPS전,응용SMT화고제소서iNOS기인가이현저제고소장융모첨단소동맥화모세혈관적홍세포류속화류량.결과표명,iNOS재내독소휴극소장미순배쇠갈적과정중발휘중요작용.
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 min after LPS injection. The results demonstrate that iNOS plays an essential role in the intestinal microcirculation disturbance which occurs in endotoxic shock.