兴奋胆碱能抗炎通路对内毒素致心肌损害的保护作用

Protective effect of cholinergic pathway excitation on heart injury after endotoxin challenge in rats

目的:研究兴奋胆碱能抗炎通路对内毒素引起大鼠心肌损害的保护作用。方法:①内毒素休克模型[静注内毒素(LPS)10mg/kg]:设手术对照组、单纯LPS组、迷走神经切断(VC)+LPS组和VC+LPS+迷走神经电刺激(VS)组,观察电刺激迷走神经对心肌组织炎症介质和心肌酶指标的影响。②内毒素血症模型(静注LPS5mg/kg):设LPS+电针非经非穴组、LPS+电针足三里穴组、VC后注射LPS组和VC+LPS+电针足三里穴组,观察电针副交感神经相关穴位足三里穴对内毒素血症引起的心肌组织损伤的保护作用。各组大鼠均于注射LPS后2h处死,检测血浆肌酸磷酸激酶同工酶(CK-MB)活性和组织病理学改变,内毒素休克各组测定心肌组织肿瘤坏死因子-α(TNF-α)含量。结果:刺激迷走神经可明显降低内毒素休克大鼠心肌组织TNF-α含量;刺激迷走神经或电针足三里穴能显著降低LPS注射后2h大鼠血浆CK-MB活性,减轻心肌组织病理损害;切断迷走神经能显著减轻或消除电针足三里穴的作用,进一步升高血浆CK-MB活性,加重心肌组织损害。结论:刺激副交感神经激活胆碱能抗炎通路对内毒素血症和内毒素休克大鼠心脏具有不同程度的保护作用。

Objective：To explore the protective effect of excitation of cholinergic nerve pathway in different ways on the heart injury in rats with endotoxin challenge. Methods： Endotoxemia and endotoxic shock were produced by intravenous injection of lipopolysaccharide （LPS,5 mg/kg or 10 mg/kg） into caudal vein. After endotoxin injection, animals were treated with either stimulation of the vagus nerve or electro-acupuncture （EA） at Zusanli. point （ST36,足三里穴）. Control animals received sham operation, or cervical vagotomy without acupuncture. The plasma MB isoenzyme of creatine kinase （CK-MB） activity was determined and cardiac histopathologie changes in animals were examined. The content of tumor necrosis factor -α （TNF-α） in heart tissue was also measured. Resuits： Excitation of the cholinergic pathway resulted in significant decrease in the content of TNF-α in heart tissue in animals with vagus stimulation,and plasma CK-MB activity reduced in animals both with vagus stimulation and EA at Zusanli point at 2 hours after endotoxin challenge,and they were correlated with milder pathologic changes in heart tissue. Vagotomy could weaken or eliminate the effects of EA,and further aggravate the elevated levels of TNF-α and CK-MB,as well as histopathologic changes compared with LPS injection alone. Conclusion： The results indicate that excitation of the cholinergic pathway by stimulation of the vagus nerve or EA at Zusanli point could protect against heart injury in rats with endotoxin challenge.