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整合素基因在膿毒癥大鼠心臟中的表達變化
畢業論文摘要:
目的：探討膿毒癥大鼠心臟中整合素基因的表達變化以及膿毒癥導致心臟損傷的相關機制。 方法：雄性3月齡Wistar大鼠12只，隨機均分為兩組，分別以盲腸結扎針刺法建立膿毒癥模型或行假手術作為對照組。術后24小時快速摘取心臟，以Langendorff 離體鼠心灌注法測量大鼠血流動力學參數后，再行病理檢查，其后以寡核苷酸基因芯片檢測整合素家族基因在兩組大鼠心臟組織中的表達差異。 結果：膿毒癥大鼠心臟無明顯病理改變，但心輸出量和每搏輸出量、心率、左心室發展壓和左室舒張末壓等血流動力學參數明顯下降，提示大鼠心臟處于抑制狀態；基因芯片檢測表明：24條整合素亞單位基因中有20條表達較對照組上調2倍以上，核心亞單位αV和β2整合素基因明顯上調，而整合素β1基因表達相對不足。 結論：膿毒癥大鼠心臟中整合素基因表達失調，αV和β2整合素基因表達上調可能促進炎性介質造成的心臟損傷；整合素β1基因表達相對不足可能與大鼠心功能不全有關。 【關鍵詞】整合素，膿毒癥，寡核苷酸基因芯片，心臟損傷
張召才，嚴靜，蔡國龍，虞意華，胡才寶
浙江醫院ICU,杭州市310013，中國
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),
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：探討膿毒癥大鼠心臟中整合素基因的表達變化以及膿毒癥導致心臟損傷的相關機制。 方法：雄性3月齡Wistar大鼠12只，隨機均分為兩組，分別以盲腸結扎針刺法建立膿毒癥模型或行假手術作為對照組。術后24小時快速摘取心臟，以Langendorff 離體鼠心灌注法測量大鼠血流動力學參數后，再行病理檢查，其后以寡核苷酸基因芯片檢測整合素家族基因在兩組大鼠心臟組織中的表達差異。 結果：膿毒癥大鼠心臟無明顯病理改變，但心輸出量和每搏輸出量、心率、左心室發展壓和左室舒張末壓等血流動力學參數明顯下降，提示大鼠心臟處于抑制狀態；基因芯片檢測表明：24條整合素亞單位基因中有20條表達較對照組上調2倍以上，核心亞單位αV和β2整合素基因明顯上調，而整合素β1基因表達相對不足。 結論：膿毒癥大鼠心臟中整合素基因表達失調，αV和β2整合素基因表達上調可能促進炎性介質造成的心臟損傷；整合素β1基因表達相對不足可能與大鼠心功能不全有關。 【關鍵詞】整合素，膿毒癥，寡核苷酸基因芯片，心臟損傷
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