Anti-endotoxic shock effects of cyproheptadine in rats  

噻庚啶抗内毒素休克的作用

作　　者：王立赞[1] 胡修周[1] 王保生[1] 朱凡河[1] 论宁[2] 张庆柱[3] 

机构地区：[1]济宁医学院病理生理学教研室,济宁272013 [2]济宁医学院生物化学教研室,济宁272013 [3]山东大学药学院药理学教研室,济南250012

出　　处：《Chinese Medical Journal》2002年第3期443-445,共3页中华医学杂志（英文版）

摘　　要：OBJECTIVE: To investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats. METHODS: Endotoxic shock was produced in rats by i.v. injection of lipopolysaccharides (LPS) (5 mg/kg). Tumor necrosis factor (TNF(alpha)) mRNA expression was assessed by Northern blot. Plasma TNF(alpha) content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca(2+)](i)) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM). RESULTS: Cyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate. Meanwhile, Cyp markedly decreased TNF(alpha) mRNA levels in rat liver (18 +/- 10 vs. LPS + saline 38 +/- 10, P目的　研究噻庚啶抗内毒素休克作用和机制。方法　静脉注射脂多糖 (LPS) 5mg/kg复制大鼠内毒素休克模型 ,Northern杂交分析TNFαmRNA表达 ,放免法测定血浆TNFα 的含量 ,黄嘌呤 黄嘌呤氧化酶法测定血浆SOD活性 ,TBA法测定血浆MDA含量 ,激光扫描共聚焦显微技术测定单细胞内游离Ca2 + 浓度 ([Ca2 + i])。结果　噻庚啶显著提高休克大鼠的平均动脉血压 (MABP)及 2 4h的存活率 ,抑制LPS诱导的大鼠肝脏TNFαmRNA的表达这 (18+ 10vsLPS +saline 38± 10 ,P <0 0 1)和血浆TNFα 水平 [(7 8± 2 4 ) μg/LvsLPS +saline (2 1 5± 3 2 )μg/L ,P <0 0 1) ],提高血浆SOD活性 [(10 37 2± 112 8)NU/LvsLPS +saline (6 15 4± 92 6 )NU/L ,P <0 0 1],降低血浆MDA的含量 [(5 2± 1 1) μmol/LvsLPS +saline (9 8± 1 5 ) μmol/L ,P <0 0 1],并能显著抑制TNFα诱导的内皮细胞 [Ca2 + ]i 升高。结论　噻庚啶通过抑制TNFα 基因表达 ,抑制脂质过氧化和防止细胞内Ca2 + 超载具有良好的抗内毒素休克作用。

关 键 词：Animals CYPROHEPTADINE Histamine H1 Antagonists MALONDIALDEHYDE RATS Rats  Wistar Research Support  Non-U.S. Gov't Shock  Septic Superoxide Dismutase Tumor Necrosis Factor-alpha 

分 类 号：R965[医药卫生—药理学]