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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。
Objective To study the anti-endotoxic effect and mechanism of thienopyrimidine. Methods LPS 5 mg / kg rat model of endotoxic shock was established. The expression of TNFαmRNA was analyzed by Northern blotting. The level of plasma TNFα was determined by radioimmunoassay. The activity of SOD was measured by xanthine oxidase method. The level of plasma MDA Content, laser scanning confocal microscopy to measure single intracellular free Ca2 + concentration ([Ca2 + i]). Results Thiagheterine significantly increased the mean arterial blood pressure (MABP) and the survival rate of 24 h in shock rats, and inhibited the LPS-induced hepatic TNFα mRNA expression (18 ± 10 vs LPS + saline 38 ± 10, P <0.01) (P <0.01), and plasma TNFα level [(78 ± 2 4) μg / L vs LPS + saline (21.5 ± 32) μg / L, P <0.01) (5 2 ± 1 1) μmol / L vs LPS + saline (9 8 ± 1 5) μmol / L vs NU / L vs LPS + saline (6 15 4 ± 92 6) NU / L, P 0 01) / L, P <0.01), and could significantly inhibit the TNFα-induced increase of [Ca2 +] i in endothelial cells. Conclusion Thiagheptamine has a good anti-endotoxic shock effect by inhibiting TNFα gene expression, inhibiting lipid peroxidation and preventing intracellular Ca2 + overload.