【摘要】 目的: 探讨丙酮酸乙酯(ethyl pyruvate, EP)对脓毒症大鼠小肠黏膜屏障的影响及其作用途径。方法: 采用盲肠结扎穿孔术（cecal ligation and puncture surgery, CLP）制备脓毒症大鼠模型。EP每6小时腹腔给药一次（120mg/kg）。统计不同组间的96小时生存率。光学显微镜观察小肠粘膜组织变化，同时观察小肠细菌移位情况，激光多普勒微循环血流计测定小肠粘膜微循环血流量、ELISA法检测肠腔内RMCPⅡ水平、分光光度法测定小肠组织髓过氧化物酶活性、半定量RT-PCR检测小肠组织诱生型一氧化氮合酶（iNOS） mRNA的表达。结果:EP提高脓毒症大鼠的生存率（37.1%比57.1%，P<0.01)。EP组小肠黏膜组织学均较Rin组显著改善；C组未发现细菌移位，EP组较Rin组细菌移位集落数明显减少﹝（26.0 ± 10.1 × 10³ ）CFUs比（14.4 ± 5.9 × 10³ ）CFUs，P<0.05﹞；Rin组小肠粘膜血流减少﹝（158.6 ± 42.9 ）PU比（269.9 ± 34.3） PU，P<0.001﹞，EP明显改善黏膜微循环血流量﹝（158.6 ± 42.9 ）PU比(199.5 ± 36.8 )PU，P<0.01﹞；Rin组小肠组织MPO较C组显著高表达MPO﹝（2.1 ± 1.9 ）U/g tissue比(12.9 ± 6.2 )U/g tissue，P<0.001﹞，EP抑制MPO高表达﹝（12.9 ± 6.2） U/g tissue比(8.6 ± 4.4 )U/g tissue，P<0.05﹞；与C组相比，Rin组中的肠腔内RMCPⅡ浓度显著增高﹝（28.6 ± 7.8 ）ng/ml比(0.9 ± 0.2) ng/ml；P<0.001﹞，EP组较Rin组未发现显著变化﹝（28.6 ± 7.8） ng/ml比 (22.7±7.9 )ng/ml，P>0.05﹞;Rin组iNOS/β-actin比值显著升高，EP治疗组中iNOS/β-actin值显著降低（0.62 ± 0.13比0.37±0.11，P<0.01）。结论: EP对脓毒症大鼠的肠道黏膜屏障有保护作用。

【关键词】 脓毒症； 丙酮酸乙酯；小肠黏膜屏障；

 

【Abstract】 Objective: To search protective effects and its mechanism of EP on the small intestine barrier in rats with sepsis. Methods:Calculated the survival rate of rats in Rin and EP groups. Histological changes in ileal architecture were observed. MLNs and spleens were collected and cultured to observed bacterial translocation. Microvascular perfusion in small intestine recorded with a laser Doppler flow monitor. Level of RMCP II released into small intestinal lumen was tested by ELISA. Small intestine tissue myeloperoxidase (MPO) activity was observed. Half-quantitative RT-PCR was used to analysis iNOS mRNA. Results: No animal died in the C group. Survival rate was 37.1% in Rin group and 57.1% in the EP group respectively. Histopathological analysis in the Rin group differed significantly from the C group. No bacterial colony was observed in the C group. The positive culture were found in the Rin group (13/13) and EP group (16/20). The bacterial colonies in the EP group significantly decreased compared with that in the Rin group .Mucosal blood flow of jejunum was observed decrease in the Rin group compared with the C group . However, mucosal perfusion of jejunum showed a significant flow increase in the EP group  compared with Rin group. Rin group showed a significant increase in the small intestine tissue levels of MPO . EP can result in a significant decrease in the activity of MPO. Expression of iNOS mRNA was not detected in jejunum of the C group. RMCP-II level in jejunal lumen of the Rin group increased significantly compared with the C group . However in the EP group, the RMCP II level hand no significant change compared with the Rin group . At 4 days after CLP, iNOS mRNA expression in jejunum of the Rin group increased significantly than that of the C group . EP blocked the iNOS mRNA expression effectively .Conclusion: EP could ameliorate sepsis mortality and protect the small intestine .

Key words：Sepsis; Ethyl pyruvate; Small intestine barrier