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整合素基因在脓毒症大鼠心脏中的表达变化

2014-11-26 02:13 毕业

摘要:

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小时快速摘取心脏，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αV和β2整合素基因明显上调，而整合素β1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，αV和β2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β1基因表达相对不足可能与大鼠心功能不全有关。 【关键词】整合素，脓毒症，寡核苷酸基因芯片，心脏损伤

 

张召才，严静，蔡国龙，虞意华，胡才宝

浙江医院ICU,杭州市310013，中国

Expression of integrin genes in heart of septic rat

ZHANG Zhao-cai*, YAN Jing, CAI Guo-long, YU Yi-hua, HU Cai-bao.

*Intensive Care Unit (ICU), Zhejiang Hospital, Hangzhou310013, China.

Corresponding author: Zhang Zhao-cai, email:zhaocai@gmail.com

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, they were treated with caecal-ligation and perforation (CLP: n=6) to establish sepsis model or sham (Sham: n=6) procedure to serve as controls. The hearts of rats were rapidly excised 24 h later. After determination of hemodynamic parameters by using Langendorff apparatus, the isolated hearts were examined histopathologically. Thereafter, expression of intergrin genes in hearts of both groups of rats were analysed by oligonucleotide microarrays. Results: In comparison with sham controls, no overt pathological changes were detected in hearts of septic rats, but decreased cardiac output (CO)(57.8±2.4 vs 29.4±3.3 ml.min-1), Stroke volume (SV) (0.18±0.01 vs 0.12±0.01 ml), heart rate (HR) (302±12 vs 256±6 bpm), Left ventricular developed pressure (LVDP) ( 90.0±2.7 vs 75.6±4.9 mmHg), LV end-diastolic pressure (LVEDP) (8.0±0.3 vs 7.5±0.3 mmHg) and Maximum rate of LV pressure rise (dP/dtmax) (2601±34 vs 2167±159 mmHg. s-1) were determined in CLP rats (P<0.01 for all), indicating that the myocardium in septic rat was depressed. Microarray analysis showed that 20 out of 24 integrin genes were up-regulated in septic rat heart by over 2 folds, among which the integrin αV and β2 gene were upregulated and integrin β1 gene was of relatively insufficient expression. Conclusion: Maladjustment in expression of integrin gene was present in septic rat heart, up-regulation of integrin αV and β2 gene might accelerate the heart injury mediated by inflammatory mediators, the relatively insufficient expression of integrin β1 gene may contribute to cardiac dysfunction in septic rat.

Key words: Integrin，Sepsis，Oligonucleotide microarray，Heart injury

摘要:

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小时快速摘取心脏，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αV和β2整合素基因明显上调，而整合素β1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，αV和β2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β1基因表达相对不足可能与大鼠心功能不全有关。 【关键词】整合素，脓毒症，寡核苷酸基因芯片，心脏损伤

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