脂多糖诱导慢性心力衰竭小鼠急性心功能恶化机制

Chronic Heart Failure Induced by Infection of Acute Deter Ioration of Cardiac Function

目的探讨脂多糖诱导慢性心力衰竭(CHF)小鼠急性心功能恶化的机制。方法 50只KM小鼠,随机分为4组,N组、NS组、HF组、HFS组,N、NS组各10只;HF、HFS组各15只。①HF、HFS组:多柔比星尾静脉注射,每次5 mg/kg,每周1次,共6周,累积总剂量30 mg/kg建立CHF模型。②NS、HFS组:第8周行尾静脉注射脂多糖致CHF急性心功能恶化。16 h后测心脏重量指数,HE染色、免疫组化测定心肌中Bax、Bcl-2、IL-6等表达水平。结果 HF组、HFS组与N、NS组比较,心脏重量指数明显增加(P<0.05);HF组心肌细胞IL-6表达最高,HFS组显著减少(P<0.05),NS组较N组明显升高;HF组Bcl-2较NS组明显升高(P<0.05);HFS组Bax较HF组明显增加(P<0.05)。结论感染致心力衰竭小鼠血浆中的IL-6过表达,同时负反馈使心肌细胞内IL-6减少致心肌细胞促凋亡基因增加。

Objective To investigate the mechanism of acute deterioration of cardiac function when chronic heart failure（CHF） induced by lipopolysaccharide. Methods 50 male KM mices were randomized 4 groups （ normal group and normal stress group, n = 10 in each group; heart failure group and Heart failure stress group, n = 15 in each group）① HF and HFS group：caudal vein injection with doxorubicin 5 mg/kg in everyweek, total time 6 weeks. ② NS and HFS group ： After 8 weeks, to lead to acute deterioration of cardiac function by caudal vein injection with lipopolysaccharide. After 16 hours we measured HWI and Bcl-2 and Bax protein expressions by hematoxylin and eosin stain and immunohistochemisty. Results Comparing HF group and HFS group to N group and NS group, HWI significantly increased（ P 〈 O. 05 ） ; Cardiac muscle cell IL-6 of HF group expression was the highest, HFS group significantly reduced （ P 〈 0.05 ）, NS group were significantly higher than N group; Bcl-2 protein of HF group were significantly higher than NS group（P 〈0.05） ;Bax protein of HFS were significantly higher than that in HF group （ P 〈 0.05 ）. Conclusion The mices with chronic heart failure induced by infection lead to IL-6 protein of blood plasma overexpression, and mean- while negative feedback reduce IL-6 of cardiac muscle cell, which lead to increasing crowded apoptosis genes of cardiac muscle cell.