已酮可可碱对脓毒症大鼠肝组织生物蝶呤及其合成限速酶表达的影响  

Effects of pentoxifylline on hepatic biopterin induction in septic rats

作　　者：董宁 姚咏明 王丽芳 于燕 陆连荣 盛志勇 

机构地区：[1]解放军第三零四医院创伤外科中心免疫研究室,北京市100037

出　　处：《中华肝胆外科杂志》2001年第7期418-421,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：国家重点基础发展规划项目(G1999054203);国家自然科学基金(39870286);军队杰出中青年人才专项基金(98J013)资助项目

摘　　要：目的探讨己酮可可碱对脓毒症大鼠肝组织生物蝶呤产生的影响及其意义。方法采用大鼠盲肠结扎穿孔(CLP)致脓毒症模型,动物随机分为正常对照组、脓毒症组和己酮可可碱治疗组。分别于 CLP 后2,8,16 h 处死动物,检测肝组织生物蝶呤及其合成限速酶—三磷酸鸟苷环水解酶Ⅰ(GTP-CH Ⅰ)mRNA 及肿瘤坏死因子-α(TNF-α)mRNA 表达的改变,同时监测血清肝功能酶学指标的变化。结果脓毒症动物肝组织生物蝶呤含量显著升高,GTP-CH Ⅰ基因表达水平也显著增强,且其改变与局部 TNF-α mRNA 表达水平呈正相关。给予己酮可可碱治疗后2 h,肝组织生物蝶呤含量、GTP-CH Ⅰ及 TNF-α mRNA 表达水平均明显下降(P<0.05),且血清谷丙转氨酶、谷草转氨酶含量也显著降低(P<0.05)。结论脓毒症早期应用己酮可可碱能有效抑制肝组织生物蝶呤及其合成限速酶基因表达,并且明显减轻脓毒症动物肝损害。Objective To investigate the potential effects of pentoxifylline on hepatic biopterin induction in a rat model of sepsis associated with intra-abdominal infection.Methods Wistar rats were subjected to sepsis induced by cecal ligation and puncture (CLP) and randomized into normal control group (n=6),sepsis group (n =18)and pentoxifylline-treated group(n=18).Animals were sacrificed at 2,8 and 16 hours after CLP. Heaptic biopterin level,guanosine triphosphate cyclohydrolase (GTP-CHI)mRNA expression and tumor necrosis factor-α(TNFα)mRNA expression were detected at various intervals.In addition,serum GPT and GOT levels were determined.Results After CLP,hepatic biopterin level and GTP-CHI mRNA expression was markedly in- creased (P<0.05-0.01),and the latter was significantly correlated to local TNFα mRNA expression (P< 0.01).Following treatment with pentoxifylline,however,tissue biopterin level,GTP-CHI gene expression and TNFα gene expression was remarkably reduced at 2 hours after CLP.Meanwhile,the levels of serum GPT and GOT were significantly decreased (P<0.05).Conclusions Early treatment with pentoxifylline has an inhibitory effect on hepatic GTP-CHI mRNA expression as well as synthesis and release of biopterin.Furthermore,it may protect liver function in rats after CLP-induced sepsis.

关 键 词：脓毒症 盲肠结扎穿孔术 生物蝶呤 己酮可可碱 肝损害 合成限速酶 

分 类 号：R631[医药卫生—外科学]