四毒清防治脂多糖性心肌损伤的机制研究

Mechanisms underlying protection of mouse myocardium against LPS-induced injury by Siduqing

目的 :观察中药复方四毒清对LPS引起的心肌损伤以及心肌TNFα和自由基生成的影响 ,探讨四毒清防治内毒素性心功能障碍的机制。方法 :将小鼠随机分成 4组 :对照组、LPS组、四毒清防治组和四毒清组 ,分别用蒸馏水和四毒清 (0 2mL/10g)灌胃 3d ,每天 2次 ,最后 1次灌胃后 2h ,腹腔注射LPS(30mg/kg)或生理盐水 (0 2mL/10g)。测定小鼠血浆肌酸激酶 (CK)、心肌超氧化物歧化酶 (SOD)的活性以及心肌TNFα和丙二醛 (MDA)的含量 ,并观察心肌组织结构和超微结构的改变。结果 :LPS注射后 12h和 2 4h ,小鼠心肌组织出现明显水肿 ,肌原纤维肿胀、排列稀疏 ,心肌间质可见少数红细胞 ;电镜观察显示 ,心肌细胞核皱缩、染色质边集 ,部分肌丝断裂 ,线粒体肿胀。四毒清防治组小鼠心肌病理改变明显轻于LPS组 ;LPS组小鼠血浆CK的活性和心肌TNFα含量明显高于对照组和四毒清防治组 ,心肌SOD活性明显低于四毒清防治组 ,而心肌MDA的含量没有显著差别 ;四毒清组和对照组比较 ,除心肌MDA含量外 ,上述其它指标没有明显差别。结论 :四毒清能减轻内毒素诱导的心肌损伤 。

AIM: To investigate the protective effect of Siduqing, a Chinese medicine, on LPS-induced myocardium injury in mice and its mechanisms. METHODS: Mice were divided into 4 group: control, LPS, Siduqing treatment and Siduqing group, and administered intragastrically with Siduqing decoction or distilled water (0 2 mL/10 g) twice a day for 3 days, two hours after Chinese herbal medicine treatment on day 3, LPS (30 mg/kg) or normal saline was injected intraperitoneally. The serum creatine kinase (CK) and myocardial superoxide dismutase (SOD) activities were determined, and myocardial tumor necrosis factor α (TNFα) and malondialdehyde (MDA) contents were also detected. In addition, the histological changes and ultrastructure of heart were examined. RESULTS: Histological examination showed edema in myocardium and architectural disarray at 12, 24 h after LPS injection, mitochondrial swelling, condensation and margination of chromatin, irregular nuclear envelope and loss of contractile filaments at 24 h post LPS administration, while Siduqing treatment attenuated the above pathological changes of myocardium. CK activity in serum and myocardial TNFα content were higher in LPS group than control and Siduqing treatment group. Myocardial SOD activity in siduqing treatment group was higher than that in LPS group, but there was no difference in myocardial MDA content between control, LPS and Siduqing treatment group. CONCLUSION: These data suggest that Siduqing protects myocardium against LPS- induced injury via inhibiting myocardial TNFα production.