脓毒症大鼠早期血管内皮和心肌损害及其相关性研究

目的观察早期脓毒症大鼠模型心脏冠状动脉内皮与心肌细胞损害情况,探讨内皮细胞在心肌损害中发挥的作用。方法 SD大鼠72只,随机分为正常、假手术和脓毒症组,采用盲肠结扎加穿孔术(CLP)制备脓毒症模型,术后3 h、6 h、12 h和24 h测量心肌力学指标,包括左室收缩峰压(LVSP)、左室压力最大上升速率(+dp/dt max)和左室压力最大下降速率(-dp/dt max),并测量血清内皮素1(ET-1)、一氧化氮(NO)、肌钙蛋白I(c Tn I)水平,透射电镜观察冠状动脉内皮细胞和心肌细胞超微结构变化。结果脓毒症组NO和ET-1水平在术后即明显升高,12 h达峰值;NO和ET-1比值在CLP术后3 h即开始明显降低,持续低于正常水平。冠状血管内皮细胞超微结构损伤呈逐步加重,管腔内脱落内皮细胞数目增多,内皮细胞超微结构损伤评分逐步增高。CLP后3 h即出现收缩舒张功能显著下降,LVSP、±dp/dt max术后6 h达最低;脓毒症组血清c Tn I在术后即明显升高,12 h时点达峰值;脓毒症组心肌细胞超微结构显示肌原纤维、肌浆网、线粒体等损伤逐渐加重,但线粒体数目有增多现象。结论脓毒症早期即存在明显冠状动脉内皮损伤,心肌细胞损害和心肌功能障碍,内皮细胞在心肌损害中可能扮演重要角色。

Study on the early vascular endothelial and myocardial damage in rats with sepsis and its correlation

Objective To observe the damages of coronary artery endothelium and myocardial damage in the rat model of early sepsis and to explore the role of endothelial cells in myocardial damage. Methods 72 SD rats were randomly divided into normal,sham-operation and sepsis groups. Cecal ligation and perforation(CLP) was used to prepare sepsis model. 3 h,6 h,12 h and 24 h after surgery,indices of myocardial mechanics were measured, including left ventricular systolic pressure (LVSP),maximum increasing rate of left ventricular pressure (+dp/dt max) and maximum decreasing rate of left ventricular pressure(-dp/dt max). The levels of endothelin 1 (ET-1),nitric oxide(NO),troponin I (cTnI)were measured. TEM was used to observe endothelial cells of coronary artery and myocardial ultrastructure changes.Results The levels of NO and ET-1 in sepsis group were increased significantly after operation and peaked at 12 hours; the ratio of NO to ET-1 was decreased significantly at 3 h after CLP,and remained below normal level. Coronary endothelial cell ultrastructure damage was gradually increased,exfoliative endoluminal endothelial cells were increased,and endothelial cell ultrastructure damage score was gradually increased. 3 h after CLP,the systolic and diastolic function was decreased significantly. LVSP,±dp/dt max reached the lowest at 6 h after operation; serum cTnI in sepsis group was increased significantly after operation and peaked at 12 h. The ultrastructure of myocardial cells in sepsis group showed that the myofibrils,sarcoplasmic reticulum,mitochondria and other damages were gradually aggravated,but there was an increase in the number of mitochondria. Conclusion In the early stage of sepsis,there are obvious coronary endothelial damage,myocardial cell damage and myocardial dysfunction. Endothelial cells may play an important role in myocardial damage.