α黑素细胞刺激素及其类似物对内毒素休克小鼠的保护作用

摘要

目的 研究α黑素细胞刺激素(α-NSH)及其类似物(NDP-MSH)对内毒素休克小鼠的保护作用。方法 腹腔注射LPS50μg/kg和D-半乳糖(D-Gal)900mg/kg复制小鼠内毒素休克模型，研究不同剂量α-MSH及NDP-MSH在不同时间或经不同途径给药对内毒素休克小鼠生存率的影响。用常规病理切片观察α-MSH对内毒素休克小鼠重要脏器病理变化的影响。结果 未给予α-MSH的内毒素休克小鼠在9h内全部死亡，经尾静脉、腹腔和皮下注射α-MSH2.5mg/kg或5.0mg/kg均可以起到一定的保护作用；给予LPS前后不同时间注射2.5mg/kgα-MSH都可以明显延长内毒素休克小鼠起始死亡的时间，提高存活率，其中以给予LPS后1h经腹腔给药疗效最好，72h的生存率达33.3%，但增加给药次数未见疗效提高。经腹腔注射2.5mg/kgNDP-MSH，小鼠平均起始死亡时间较α-MSH组延长4h，72h的生存率升至44.4%。病理学检查结果表明ɑ-MSH可以减轻LPS引起的肝脏、脾脏及肺脏瘀血及细胞坏死。结论 α-MSH及NDP-MSH可以减轻LPS引起的小鼠重要脏器的病理损害，对内毒素休克小鼠有明显的保护作用。%Objective To study the protective effects of a melanocytestimulating hormone (α-MSH)and its analogue (NDP-MSH)on endotoxic shock mice.Methods The mice were given an intraperitoneal injection of LPS 50 μg/kg and D-Galactosamine 900 mg/kg to reconstruct the endotoxic shock models.The survival rate of endotoxic shock mice was observed after treated by different doses of ɑ-MSH or NDP-MSH through different ways or at different times.The pathologic changes of important organs from the endotoxic shock mice were inspected by routine tissue slice.Results The lethality of endotoxic shock mice which were not given α-MSH was 100% within 9 h. α-MSH (2.5 mg/kg or 5.0 mg/kg) given through caudal vein,peritoneal or subcutaneous ways could reduce the lethality of endotoxemia shock mice and the intraperitoneal injection was the most effective way.The delayed intial death time and the increased survival rate appeared in endotoxic shock mice treated by ip α-MSH 2.5 mg/kg at different times.The most effective time administrating α-MSH to the mice was 1 h after giving LPS.The survival rate of endotoxic shock mice treated by ip α-MSH 2.5 mg/kg 1 h after giving LPS arrived 33.3% within 72 h,but the protective effect of α-MSH was not enhanced by increasing the frequency of administration.In endotoxic shock mice treated by ip NDP-MSH 2.5 mg/kg,the mean time of intial death was delayed 4 h compared with ɑ-MSH group and the survival rate arrived 44.4% within 72 h. The results of pathologic inspection showed that α-MSH could lighten the blood stasis and the cytonecrosis of livers,spleens or lungs caused by LPS.Conclusion α-MSH or NDP-MSH can ease the pathologic damage of mouse important organs caused by LPS and have distinct protective effect on endotoxic shock mice.