整合素基因在脓毒症大鼠心脏中的表达变化

Expression of integrin genes in heart of septic rat

目的探讨脓毒症大鼠心脏中整合素基因的表达变化以及脓毒症导致心脏损伤的相关机制。方法雄性3个月龄 Wistar 大鼠12只,随机均分为两组,分别以盲肠结扎针刺法建立脓毒症模型或行假手术作为对照组。术后24 h 快速摘取心脏,以 Langendorff 离体鼠心灌注法测量大鼠血流动力学参数后,再行病理检查,其后以寡核苷酸基因芯片检测整合素家族基因在两组大鼠心脏组织中的表达差异。结果脓毒症大鼠心脏无明显病理改变,但心输出量和每搏输出量、心率、左心室发展压和左室舒张末压等血流动力学参数明显下降,提示大鼠心脏处于抑制状态;基因芯片检测表明:24条整合素亚单位基因中有20条表达较对照组上调2倍以上,核心亚单位α_v和β_2整合素基因明显上调,而整合素β_1基因表达相对不足。结论脓毒症大鼠心脏中整合素基因表达失调,α_v 和β_2整合素基因表达上调可能促进炎性介质造成的心脏损伤;整合素β_1基因表达相对不足可能与大鼠心功能不全有关。

Objective To investigate the expression profile of integrin genes in heart of septic rat and relevant mechanisms responsible for sepsis-induced heart injury. Methods Twelve 3-month-old male Wistar rats were randomized to 2 equal groups, sepsis model group （ CLP group） undergoing ligation and perforation with needle of the distal caecum so as to establish sepsis model, and sham operation group （ Sham group） , undergoing sham operation only serve as controls. Twenty-four later the hearts of rats were rapidly excised. After determination of the hemodynamic parameters by using Langendorff apparatus, the isolated hearts were cut into 2 parts vertically to undergo histopathological examination and analysis of the expression of integrin genes by oligonucleotide microarrays respectively. Results No overt pathological changes were detected in the hearts of septic rats, however, the cardiac output, stroke volume, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, and maximum rate of left ventricular pressure rise of the CLP group were 29.4 ±3.3 ml/min, 0. 12 ±0.01 ml, 256 ±6 bpm, 75.6 ±4.9 mm Hg, 7.5 ± 0.3 mm Hg, and 2167 ±159 mm Hg/s respectively, all significantly than those of the Sham group （57.8 ±2.4 ml/min, 0. 18 ±0. 01 ml, 302 ± 12 bpm, 90. 0 ±2. 7 mmHg, 8.0 ±0. 3 mmHg. and 2601 ± 34 mmHg/s respectively, all P 〈 0. 01 ）. Microarray analysis showed that 20 out of 24 integrin genes were up-regulated by more than 2 times in the septic rat heart, among which the integrin αv and β2 genes were upregulated and the expression of integrin β1 gene was relatively insufficient. Conclusion Maladjustment in expression of integrin genes is present in the septic rat heart. Up-regulation of integrin αv and β2 genes may accelerate the heart injury mediated by inflammatory mediators, and the relatively insufficient expression of integrin β1 gene may contribute to cardiac dysfunction.