轻度CLP模型大鼠在脓毒症早期即发生心肌收缩与舒张功能障碍

目的:利用轻度盲肠结扎穿孔术(CLP)复制脓毒症大鼠模型,比较脓毒症大鼠心功能与其它器官功能障碍发生的时间。方法:将大鼠随机分为假手术组和盲肠结扎穿孔术组,分别于手术后6 h、9 h和12 h用Langendorff装置检测大鼠心肌收缩与舒张功能,并测定心肌肿瘤坏死因子α(TNF-α)、细胞间黏附分子1(ICAM-1)和血管内皮细胞黏附因子1(VCAM-1)的表达;同时检测血清TNF-α水平以及大鼠肝、肾功能和肺湿/干重比值。结果:轻度CLP术后10 d,大鼠的死亡率为26.7%。CLP术后9 h与12 h左心室内压最大上升与下降速率显著低于假手术组;CLP术后6 h,心肌TNF-α、ICAM-1和VCAM-1的mRNA表达显著高于假手术组,CLP术后9 h心肌TNF-α和VCAM-1的蛋白表达显著升高。CLP术后9 h血清天冬氨酸氨基转移酶活性和12 h丙氨酸氨基转移酶活性高于假手术组。而术后6 h、9 h和12 h,大鼠血尿素氮水平、肺湿/干重比与相应时点的假手术组比较,差异没有统计学显著性。结论:轻度CLP模型大鼠在脓毒症发生后6 h心肌炎症因子表达增多,9 h后即发生心肌内在收缩与舒张功能障碍,其发生早于肝、肾功能损伤。

Presence of intrinsic myocardial systolic and diastolic dysfunctions at early stage of sepsis in mild CLP rats

AIM: To observe the time pattern of intrinsic myocardial dysfunction and other organ dysfunction in a rat model of mild cecal ligation and puncture (CLP).METHODS: Male SD rats were randomly divided into sham group and CLP group. At 6 h, 9 h and 12 h after sham operation or CLP, intrinsic myocardial systolic and diastolic functions were determined by Langendorff system. The expression of cardiac tumor necrosis factor (TNF)-α, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was measured. In addition, serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as blood urea nitrogen (BUN) were analyzed. For evaluating pulmonary edema, the lung wet-dry weight (W/D) ratio was calculated.RESULTS: In mild CLP rats, the mortality rate was 26.7% on day 10 after CLP. At 9 h and 12 h after CLP, the maximum rate of positive and negative changes in left ventricular pressure (±dp/dt) were decreased in CLP group compared with sham group. At 6 h after CLP, cardiac mRNA expression of TNF-α, ICAM-1 and VCAM-1 was increased in septic rats compared with the controls. At 9 h after CLP, cardiac protein levels of TNF-α and VCAM-1 were higher in CLP group than that in sham group (P<0.05). The serum AST activity at 9 h and ALT activity at 12 h after CLP were increased in CLP group compared with sham group. However, no difference in BUN and lung W/D ratio at 6 h, 9 h and 12 h between CLP group and sham group was observed.CONCLUSION: Our findings highlight the presence of intrinsic myocardial dysfunction at 9 h after CLP in a rat model of mild CLP. Intrinsic myocardial dysfunction occurs earlier than the liver and kidney dysfunctions.