热休克蛋白A12B对内毒素血症所致心功能不全的保护作用

目的探讨高表达热休克蛋白A12B（HSPA12B）对内毒素血症所致心功能不全的影响。方法 （1）采用western blot法鉴定HSPA12B在HSPA12B转基因（HSPA12B Tg）鼠心脏中的表达;（2）HSPA12B Tg和野生型（WT）对照鼠均腹腔注射内毒素（LPS）10mg/kg,6h后以超声心动图测定心功能;（3）LPS注射后6h,收集心脏,石蜡切片,HE染色,分析组织水肿和白细胞浸润程度。结果 （1）HSPA12B Tg鼠心肌组织中HSPA12B表达较WT鼠升高12倍（P〈0.01）;（2）LPS使WT和HSPA12B Tg鼠心功能均显著下降,但与WT鼠比较,HSPA12BTg鼠的心功能显著改善（P〈0.01）,射血分数（EF）增加了56.0%,缩短分数（FS）增加了72.5%;（3）LPS使WT和HSPA12B Tg鼠心肌间质中白细胞浸润,但与WT鼠比较,HSPA12B Tg鼠的心肌间质中白细胞浸润数量显著减少45.1%（P〈0.05）。结论 HSPA12B高表达显著抑制内毒素血症所致的心功能不全、减轻白细胞在心肌间质的浸润程度。

Protective effects of heat shock protein A12B on cardiac function in mice during endotoxemia

Objective To examine the effect of heat shock protein A12B(HSPA12B)on cardiac dysfunction during endotoxemia in mice.Methods Transgenic mice with overexpression of human HSPA12B gene(HSPA12B Tg)and age-matched wild type(WT)mice were injected with lipopolysaccharide(LPS,10 mg/kg).The overexpression of HSPA12B gene was examined by western blot.Six hours after LPS injection,cardiac functions were evaluated by echocardiography and neutrophils infiltration was examined by histological study.Results The protein levels of HSPA12B was increased by 12 folds in the hearts of HSPA12B Tg mice compared with WT mice.LPS administration significantly decreased cardiac function in WT mice.In HSPA12B Tg mice,LPS-induced cardiac dysfunction was significantly attenuated compared with LPS-treated WT mice.HSPA12B Tg mice showed less neutrophils infiltration into myocardial interstitial compared with WT mice following LPS treatment.Conclusions The results suggest that HSPA12B plays an important role in attenuation of cardiac dysfunction in endotoxemia and that the mechanisms of the protection may involve inhibition of neutrophils infiltration.