Dextran-40对致命性水母蜇伤的保护作用

摘要

目的 分析低分子右旋糖酐(Dextran-40)对致命性水母蜇伤的保护作用.方法 首先,应用本课题组建立的致命性水母蜇伤综合征(acute jellyfish envenomation syndrome,AJES 和 delayed jellyfish envenomation syndrome,DJES)模型,在整体动物水平分别观察Dextran-40对AJES小鼠生存率的影响、AJES大鼠循环功能的影响以及DJES大鼠血生化指标的影响.然后,应用激光扫描共聚焦显微镜,在细胞水平观察Dextran-40对发形霞水母触手提取物(tentacle extract,TE)所致心肌细胞损伤的保护作用.结果 整体动物水平研究结果发现,Dextran-40 0.8g/kg能显著降低TE所致AJES小鼠死亡率;Dextran-40 0.6g/kg能明显缓解TE所致AJES大鼠的血压下降,改善TE所致DJES大鼠的肝功能指标(ALT,AST,A/G)、心肌损伤相关酶指标(CK,LDH).细胞水平研究结果表明,Dextran-40 5μg/mL显著抑制TE引起的心肌细胞内Ca2+增加和心肌细胞死亡.结论 Dextran-40对致命性水母蜇伤的保护作用可能与其稳定血压或者封堵水母毒素在细胞膜上形成的孔道有关.因为Dextran-40属临床常用药物,故推荐Dextran-40作为水母蜇伤的急救药.%Objective To investigate the protective effects of Dextran-40 on fatal jellyfish stings at whole animal and cellular levels.MethodsFirstly, using the fatal jellyfish envenomation syndrome (acute jellyfish envenomation syndrome, AJES and delayed jellyfish envenomation syndrome, DJES) models established earlier by ourselves, we surveyed the effects of Dextran-40 on the survival rate of AJES mice, on the circulatory function of AJES rats and on the serum biochemical indexes of DJES rats.In addition, the protective effects of Dextran-40 on cardiomyocytes against the damage induced by tentacle extract (TE) from the jellyfish Cyanea capillata were studied at the cellular level by laser scanning confocal microscopy.ResultsAt the whole animal level, Dextran-40 at 0.8g/kg significantly improved the survival rate of AJES mice, and at 0.6g/kg greatly inhibited the drop of blood pressure of AJES rats.For the DJES rats, Dextran-40 at 0.6g/kg had a significant protective effect on the liver function indexes (ALT, AST, A/G) and myocardial enzymes (CK, LDH).At the cellular level, Dextran-40 5μg/mL greatly inhibited the TE-induced increase in intracellular Ca2+ content and the death of cardiomyocytes.ConclusionThe protective effects of Dextran-40 on fatal jellyfish stings may be related to its ability to stabilize blood pressure or block the TE-induced pore formation in the cardiomyocytes.Considering that the clinical safety of Dextran-40, we strongly recommend it as a first-aid medicine for jellyfish stings.