肠源性内毒素血症在代谢综合征相关的动脉粥样硬化所致的心肌损伤研究

目的探讨肠源性内毒素血症在代谢综合征相关的动脉粥样硬化所致的心脏损伤的发生机制。方法 SD大鼠64只随机分为对照组和模型组,各32只;每组再随机分为3月、6月、9月、12月4个时段进行实验观察,每时段8只。对照组喂饲基础饲料,模型组喂饲高糖高脂饲料。应用放免法及酶联免疫吸附实验测定外周血内毒素及相关的炎症介质肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、巨噬细胞趋化蛋白-1(MCP-1)的表达以及甘油三酯、总胆固醇、游离脂肪酸、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖、空腹胰岛素的表达;并观察主动脉及心脏病理形态学变化;免疫组织化学染色CD68及Tunnel观察巨噬细胞在心肌的浸润及心肌凋亡情况;苏丹IV特殊染色观察脂质在心肌细胞内和心肌肌束间的异位沉积情况。结果模型组大鼠从第3月即发生了内毒素血症和胰岛素抵抗;同时出现了中心性肥胖、脂代谢紊乱、高血糖症及高胰岛素血症等代谢综合征,病理形态学显示模型组随鼠龄增加,主动脉发生脂质异位沉积及典型的动脉粥样斑块的形成;心肌细胞内及心肌肌束间于第6个月出现显著的脂质沉积,在第9～12月加重至严重程度,心肌细胞凋亡于6月组明显发生,第9～12月组发生较广泛凋亡。结论高糖高脂膳食可诱导肠源性内毒素血症和胰岛素抵抗的发生,可能在代谢综合征及其相关的疾病如动脉粥样硬化及其相关的心肌损伤中起重要作用。

Research of effect of IETM on cardiopathy caused by atherosclerosis relevant to metabolism syndrome

Objective To research the effect of IETM on cardiopathy caused by atherosclerosis relevant to metabolism syndrome.Methods Sixty-four SD rats were randomly divided into two groups: normal control group with normal basic diet and model group with high sucrose and high fat diet.Each group were thirty-two rats and divided four phases:three months,six months,nine months and twelve months.Each phase had eight rats.Using radioimmunoassay and ELISA detect endotoxin(LPS) and associative inflammatory media TNF-a,CRP,MCP-1,the triglyceride,cholesterol,fasting free fatty acid,high-density lipoprotein,low-density lipoprotein,plasm glucose(FPG) and fasting insulin(FINs).All the rats were killed and their aorta,and cardiac were taken to carry on HE stain for observing their histopathologic and morphologic change.Tunnel was used to detect the cardiac muscle cells apoptosis by immunohistochemistry.The expression of CD68 protein were detected by immunohistochemistry for observing mononuclear cells expression in cardiac muscle.Sudan IV stain was used to show whether ectopic lipid have accumulated in cardiac muscle.Results There is the high level of LPS in plasma of model group of 3month,and aorta had ectopic lipid moreover formed the tipical atheromatous plaque.The ectopic lipid occured in cardiac muscle cells in model group rats of 6 month,and became critically in model rats from 9 to 12 month,the apoptosis of cardiac muscle cells took place prominently in n model group rats of 6 month and occured widely in model rats from 9 to 12 month.Conclusions High-fat high-sucrose diet induces intestinal endotoxemia and insulin resistance,which play an important role in metabolic syndrome and metabolic diseases such as atherosclerosis and cardiopathy accompanied by atherosclerosis.