小鼠肝脏持续低灌注模型的建立及其对热缺血再灌注损伤的耐受性

发布时间：2018-03-23 09:52

本文选题：肝脏低灌注　切入点：缺血　出处：《第二军医大学学报》2016年05期

【摘要】：目的建立一种稳定的小鼠肝脏持续低灌注模型,并在此基础上研究肝脏持续低灌注对小鼠肝脏热缺血再灌注损伤的影响。方法选用6~8周龄C57BL/6小鼠建模,将门静脉缩窄至1mL注射器针头直径,门静脉缩窄后3d、7d、14d和21d行肝功能及肝脏组织病理学检测;选用稳定的模型小鼠行70%缺血再灌注手术,再灌注3h、24h、48h后行肝功能及肝脏组织病理学检测。对照组采用正常C57BL/6小鼠行缺血再灌注手术。结果小鼠门静脉缩窄术后,丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)均有不同程度的升高,在7d时达到高峰[ALT:(60.8±6.2)U/L vs(25.5±2.8)U/L,P0.001;AST:(74.9±6.1)U/L vs(39.1±3.2)U/L,P0.001),同时H-E染色显示7d时肝细胞损伤最重,并且有较多炎细胞浸润;在21d时,ALT基本恢复正常水平(P0.05),而AST仍高于正常水平(P=0.03)。低灌注处理7d的小鼠进行缺血再灌注手术后,肝酶和组织病理学检查显示肝细胞损伤较对照组显著加重,肝酶在再灌注3h达到高峰[ALT:(8 217.0±1 111.8)U/L vs(5 597.4±1 015.3)U/L,P=0.004;AST:(8 548.2±1 155.4)U/L vs(5 765.4±956.9)U/L,P=0.003];再灌注48h时,对照组小鼠ALT和AST均恢复正常,而经过低灌注处理的小鼠肝酶仍高于对照组[ALT:(608.8±442.9)U/L vs(47.4±20.1)U/L,P=0.008;AST:(861.8±442.8)U/L vs(70.8±68.3)U/L,P=0.008)。结论成功建立了稳定的小鼠肝脏持续低灌注模型,经持续低灌注处理后的肝脏对热缺血再灌注损伤的耐受能力显著降低,这在一定程度上能够模拟临床上心死亡器官捐献供肝的状况。
[Abstract]:Objective to establish a stable model of liver continuous low perfusion in mice, and to study the effect of continuous low perfusion of liver on liver warm ischemia reperfusion injury in mice. Methods C57BL/6 mice at the age of 6 weeks and 8 weeks were used to model the model. The portal vein was constricted to the needle diameter of 1mL syringe, the liver function and hepatic histopathology were detected at 14 days and 21 days after portal vein coarctation, and 70% ischemia reperfusion operation was performed in stable model mice. Liver function and liver histopathology were detected after 3 h, 24 h and 48 h after reperfusion. Normal C57BL/6 mice were treated with ischemia reperfusion. Results after portal vein coarctation, alanine aminotransferase (alt) and aspartate aminotransferase (AST) increased in varying degrees. On the 7th day, the peak was reached [ALT:(60.8 卤6.2)U/L vs(25.5 卤2.8 U / L] P 0.001 + AST: 74.9 卤6.1)U/L vs(39.1 卤3.2U / L P 0.001.The H-E staining showed that the liver cells were most damaged and had more inflammatory cell infiltration on the 7th day. On the 21st day, alt returned to normal level basically, while AST was still higher than the normal level. Liver enzyme and histopathological examination showed that liver cell injury was significantly more serious than that of control group after ischemia reperfusion operation in mice treated with low perfusion for 7 days. The hepatic enzyme reached its peak at 3 h after reperfusion [ALT:(8 217.0 卤1 111.8)U/L vs(5 597.4 卤1 015.3U / L] [ALT:(8: 8 548.2 卤1 155.4)U/L vs(5 765.4 卤956.9 vs(5 765.4 卤956.9U / L P0. 003], and the ALT and AST of the control group returned to normal at 48 h after reperfusion. However, the liver enzyme of mice treated with low perfusion was still higher than that of the control group [ALT:(608.8 卤442.9)U/L vs(47.4 卤20.1U / L ~ (-1) U / L] P _ (0.008) vs(70.8 ~ 861.8 卤442.8)U/L vs(70.8 卤68.3U / L ~ + P _ (0.008) .Conclusion A stable model of liver continuous low perfusion was established successfully, and the tolerance of liver treated with continuous low perfusion to hot ischemia / reperfusion injury was significantly decreased. To some extent, this can mimic the clinical status of donor liver donation of cardiac death organs.
【作者单位】：第二军医大学长征医院肝脏外科解放军器官移植研究所;浙江大学医学院附属邵逸夫医院头颈外科;第二军医大学基础部免疫学教研室;
【基金】：国家自然科学基金(81470900) 上海市自然科学基金(15ZR1414100)~~
【分类号】：R575;R-332

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