抗菌药物对酒精性肝病创伤弧菌脓毒症大鼠肝组织Toll样受体及髓样分化蛋白2表达的影响  

Effects of antimicrobial agents on the Toll like receptors and myeloid differentiation protein-2 in liver tissue of alcohol-induced liver disease： experiment with rats

作　　者：卢中秋[1] 李萌芳[1] 梁欢[1] 邱俏檬[1] 周铁丽[2] 洪广亮[1] 刘刚[1] 

机构地区：[1]温州医学院附属第一医院,325000 [2]温州医学院附属第一医院临检中心,325000

出　　处：《中华医学杂志》2009年第2期138-141,共4页National Medical Journal of China

基　　金：浙江省医学扶植重点建设学科基金（07-F04）;浙江省科技厅科研基金（2005C30009）;温州市科技局重大计划基金（Y2004A004）

摘　　要：目的探讨酒精性肝病大鼠创伤弧菌（VV）脓毒症肝组织Toll样受体及髓样分化蛋白2的表达及其动态变化。方法制作酒精性肝病大鼠VV脓毒症模型和酒精性肝病VV脓毒症抗菌药物治疗模型。大鼠随机分为正常对照组（N组）、酒精性肝病对照组（A组）、酒精性肝病抗菌药物对照组（AA组）、酒精性肝病VV脓毒症组（AV组）和酒精性肝病VV脓毒症抗菌药物治疗组（AVA组）。采用逆转录聚合酶链反应（RT—PCR）技术检测各组大鼠不同时问点肝组织TLR2、TLR4、MD-2 mRNA表达及其动态变化。结果AV组大鼠在染菌后2h，TLR2、TLR4、MD-2 mRNA表达开始升高（0．56±0．08、0．70±0．08±0．59±0．05），12h达峰（0．85±0．18、0．92±0．13、0．83±0．11），染菌后24h下降。染菌后各时间点TLR2、TLR4、MD-2 mRNA表达较N组及A组显著升高（P〈0.05或P〈0．01），AVA组TLR2、TLR4、MD-2 mRNA与各相同时间点AV组相比，表达量明显降低（6h：0．48±0．10、0．60±0．06、0．56±0．07；12h：0．45±0．13、0．59±0.11、0．57±0．12；24h：0．45±0．13、0．51±0．12、0．45±0．14）（P〈0．05或P〈0．01）。结论酒精性肝病大鼠VV脓毒症肝组织TLR2、TLR4、MD-2 mRNA表达水平随脓毒症病情的进展而升高，其与脓毒症的发生、发展密切相关。应用足量头孢哌酮钠和乳酸左氧氟沙星能显著降低肝组织TLR2、TLR4、MD-2 mRNA的表达，对酒精性肝病VV脓毒症大鼠有明显的治疗作用。动态监测TLR2、TLR4、MD-2 mRNA改变对VV脓毒症发病及治疗过程具有一定的意义。Objective To investigate the effects of antimicrobial agents on the Toll like receptors （TLRs） and myeloid differentiation protein （MD）-2 in liver tissue of alcohol-induced liver disease with Vibrio vulnificus （VV） sepsis. Methods Eighty SD rats were randomly divided into 2 groups： alcohol gastric lavage group （ n = 74 ） undergoing alcohol gastric perfusion once a day for 10 weeks and normal control group （ Group N, n = 6）. 66 surviving rats in the gastric perfnsion group were randomly divided into 6 equal subgroups： Subgroup A was alcohol-induced liver disease control subgroup. Subgroup AA, alcohol- induced liver disease and antibacterial drug control subgroup, underwent intraperitoneal injection of cefoperazone sodium and levofloxacin （LVFX）, The other 9 subgroups underwent subcutaneous injection of VV to establish animal model of VV sepsis, the rats of 4 of which were killed 2, 6, 12, and 24 h later respectively with their livers taken out （ Subgroups AV）, and the rats of 5 of which underwent intraperitoneal injection of cefoperazone sodium and LVFX 4 h after VV injection twice a day（ Subgroups AVA） and were killed 6, 12 , 24 , 36 h, and 1 week later with their livers taken out. The behavioral changed were observed. PCR was used to detect the mRNA expression of TLR2, TLR4, and MD-2 Results The mRNA expression levels of TLR2, TLR4, and MD-2 in liver 2, 6, 12, and 24 h after in Subgroups AV were all significantly higher than those of Group N （P 〈 0.05 or P 〈 0.01 ） with the maximum level in the AV-12 h subgroup. The mRNA expression levels of TLR2, TLR4, and MD-2 in liver 6 h, 12 h, and 24 h after the VV injection of Subgroup AVA were all significantly lower than those of Group AV （ P 〈 0.05 or P 〈 0.01 ）. Conclusion The mRNA expression levels of TLR2, TLR4, and MD-2 in liver tissue of alcohol-induced liver disease with VV sepsis, which may be reduced by treatment of cefoperazone sodium and LVFX, are associated with the development of VV sepsis. This treatment i

关 键 词：酒精性肝病 创伤弧菌 脓毒症 TOLL样受体 髓样分化蛋8-2 

分 类 号：R686[医药卫生—骨科学]