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抗菌药物对创伤弧菌脓毒症诱导的酒精性肝病大鼠肝组织中 toll 样受体和炎症细胞因子的影响。

Effect of antimicrobial agents on the toll-like receptors and inflammatory cytokines in liver tissue of the alcohol-induced liver disease in rats with Vibrio vulnificus sepsis.

机构信息

Department of Emergency, First Affiliated Hospital of Wenzhou Medical College, Zhejiang, China.

出版信息

Chin Med J (Engl). 2009 Aug 20;122(16):1910-6.

PMID:19781370
Abstract

BACKGROUND

Septicemia and inflammation-mediated septic shock caused by Vibrio vulnificus (VV) is strongly associated with chronic liver disease. This study examined the effects of antimicrobial therapy on expression of hepatic toll-like receptors and inflammatory cytokines in rats with alcohol-induced liver disease complicated by VV sepsis.

METHODS

Male Sprague-Dawley rats were assigned to the following treatment groups: normal control (N), alcoholic liver disease control (A), antimicrobial-treated alcoholic liver disease control (AA), alcoholic liver disease with VV sepsis (AV), and antimicrobial-treated alcoholic liver disease with VV sepsis (AVA). Alcohol-induced liver disease was observed in all groups except N. Expression of mRNAs encoding hepatic toll-like receptors 2 and 4, myeloid differentiation protein-2, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and IL-10 was determined by RT-PCR.

RESULTS

mRNAs encoding toll-like receptors 2 and 4 and myeloid differentiation protein-2 were significantly up-regulated in group AV as compared to control groups at 2 - 24 hours of sepsis; peak expression occurred at 12 hours. These mRNAs were also up-regulated in group AVA but to lesser degrees than in group AV at comparable time post-infection. mRNAs encoding TNF-alpha, IL-1beta and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-alpha and IL-1beta mRNAs was lower at 12 - 24 hours post-infection and expression of IL-6 mRNA was lower at 24 hours post-infection. Compared with control groups, IL-10 mRNA expression in group AV was markedly higher at 12 - 24 hours of sepsis. Expression of IL-10 mRNA was lower in group AVA as compared to AV at 24 hours of sepsis.

CONCLUSIONS

Antimicrobial therapy reduces expression of toll-like receptors and cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Monitoring hepatic toll-like receptor and cytokine expression during antibiotic therapy may be valuable for determining the course of VV sepsis in subjects with liver disease.

摘要

背景

创伤弧菌(Vibrio vulnificus,VV)引起的败血症和炎症介导的感染性休克与慢性肝病密切相关。本研究检测了抗菌治疗对酒精性肝病合并 VV 败血症大鼠肝组织 toll 样受体和炎症细胞因子表达的影响。

方法

雄性 Sprague-Dawley 大鼠分为以下治疗组:正常对照组(N)、酒精性肝病对照组(A)、抗菌治疗的酒精性肝病对照组(AA)、酒精性肝病合并 VV 败血症组(AV)和抗菌治疗的酒精性肝病合并 VV 败血症组(AVA)。除 N 组外,其余各组均建立酒精性肝病模型。采用 RT-PCR 检测肝组织 toll 样受体 2 和 4、髓样分化蛋白-2、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-10(interleukin-10,IL-10)mRNA 的表达。

结果

与对照组相比,败血症 2-24 小时 AV 组肝组织 toll 样受体 2 和 4、髓样分化蛋白-2 mRNA 表达显著上调,12 小时达高峰;AVA 组也显著上调,但上调幅度低于 AV 组。AV 组 TNF-α、IL-1β和 IL-6 mRNA 表达随感染而升高。与 AV 组比较,AVA 组感染后 12-24 小时 TNF-α和 IL-1β mRNA 表达降低,24 小时 IL-6 mRNA 表达降低。与对照组相比,败血症 12-24 小时 AV 组 IL-10 mRNA 表达显著升高。AVA 组 IL-10 mRNA 表达低于 AV 组。

结论

抗菌治疗可降低酒精性肝病合并 VV 败血症大鼠肝组织 toll 样受体和细胞因子的表达。监测肝病患者抗生素治疗过程中肝组织 toll 样受体和细胞因子的表达,可能有助于判断 VV 败血症的病程。

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