赛庚啶对大鼠抗内毒素休克的作用

Anti-endotoxic shock effects of cyproheptadine in rats.

作者信息

Wang Lizan, Zhang Qingzhu, Hu Xiuzhou, Lun Ning, Wang Baosheng, Zhu Fanhe

机构信息

Department of Pathophysiology, Jining Medical College, Jining 272013, China.

出版信息

Chin Med J (Engl). 2002 Mar;115(3):443-5.

PMID:11940385

Abstract

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+)) 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 < 0.01) as well as plasma TNF(alpha) content [(7.8 +/- 2.4) microg/L vs. LPS + saline (21.5 +/- 3.2) microg/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) micromol/L vs. LPS + saline (9.8 +/- 1.5) micromol/L, P < 0.01], and inhibited TNF(alpha)-induced Ca(2+) elevation.

CONCLUSION

Cyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing Ca(2+) overload.

摘要

目的

研究赛庚啶（Cyp）对大鼠内毒素休克的拮抗作用及其机制。

方法

通过静脉注射脂多糖（LPS）（5mg/kg）制备大鼠内毒素休克模型。采用Northern印迹法评估肿瘤坏死因子（TNFα）mRNA表达。用放射免疫分析法测定血浆TNFα含量。检测血浆超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。用激光扫描共聚焦显微镜（LSCM）测定单个内皮细胞内游离钙浓度（[Ca²⁺]i）。

结果

静脉注射LPS后立即注射5mg/kg Cyp可提高休克大鼠的平均动脉血压（MABP），并改善其24小时生存率。同时，Cyp显著降低大鼠肝脏中TNFα mRNA水平（18±10 vs LPS+生理盐水38±10，P<0.01）以及血浆TNFα含量[（7.8±2.4）μg/L vs LPS+生理盐水（21.5±3.2）μg/L，P<0.01]。它增强了血浆SOD活性[（1037.2±112.8）NU/L vs LPS+生理盐水（615.4±92.6）NU/L，P<0.01]，降低了MDA含量[（5.2±1.1）μmol/L vs LPS+生理盐水（9.8±1.5）μmol/L，P<0.01]，并抑制了TNFα诱导的[Ca²⁺]i升高。