摘要目的　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) 5 mg/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24 h的存活率,抑制LPS诱导的大鼠肝脏TNFα mRNA的表达这(18+10 vs LPS+saline 38±10, P<0.01)和血浆TNFα水平［（7.8±2.4)μg/L vs LPS+saline (21.5±3.2)μg/L,P<0.01)］,提高血浆SOD活性［（1037.2±112.8）NU/L vs LPS+saline (615.4±92.6)NU/L,P<0.01］,降低血浆MDA的含量［（5.2±1.1)μmol/L vs LPS+saline (9.8±1.5)μmol/L, P<0.01］,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.

abstractsObjective To investigate the antagonistic effect and mechnism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats. Methods Endotoxic shock was produced in rats by iv injection of lipopolysaccharides (LPS) (5?mg/kg). Tumor necrosis fator (TNFα) mRNA expression was assessed by Northern blot. Plasma TNFα content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca2+]i) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM). Results Cyp 5?mg/kg injected immediately after iv LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24?h survival rate. Meanwhile, Cyp markedly decreased TNFα mRNA levels in rat liver (18±10 vs LPS+saline 38±10, P<0.01) as well as plasma TNFα content [(7.8±2.4) μg/L vs LPS+saline (21.5±3.2) μg/L, P<0.01)]. It enhanced plasma SOD activity [(1037.2±112.8) NU/L vs LPS+saline (615.4±92.6) NU/L, P<0.01], reduced the MDA content [(5.2±1.1) μmol/L vs LPS+saline (9.8±1.5) μmol/L, P<0.01], and inhibited TNFα-induced [Ca2+]i elevation. Conclusion Cyp exerts an anti-endotoxic shock effect by inhibiting TNFα gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca2+]i overload.