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雷帕霉素在肝缺血再灌注损伤中对自噬相关蛋白ULK1、LC3表达的影响
Effect of rapamycin on the expression of autophagy-related proteins Unc-51 like autophagy activating kinase 1 and microtubule-associated protein 1 light chain 3 in hepatic ischemia-reperfusion injury and its significance
文章发布日期:2019年09月05日  来源:  作者:杨龙灿,张旭阳,潘宁波,等  点击次数:129次  下载次数:18次

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【摘要】: 目的 研究雷帕霉素在肝脏缺血再灌注损伤中对自噬相关蛋白ULK1、LC3表达的影响及意义。方法 建立3组大鼠肝脏缺血再灌注损伤模型,实验组(n=10)、对照组(n=10)、假手术组(n=10)。分别于术后24、72 h取材:检测血清ALT和AST水平、肝脏病理以及ULK1、LC3 mRNA水平、蛋白水平。计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验。结果 肝脏缺血再灌注损伤24 h后血清ALT、AST水平升高,肝脏病理结构损伤(F值分别为1531.83、1799.97,P值均<0.05),实验组血清ALT[(354.58±28.40)U/L vs (556.15±19.32)U/L]、AST[(384.37±8.98)U/L vs (575.96±30.21)U/L]水平较对照组降低(P值均<0.05),肝脏病理结构损伤减轻;术后72 h后实验组血清ALT[(271.81±8.63)U/L vs (466.33±30.00)U/L]、AST[(358.92±13.20)U/L vs (497.05±40.14)U/L]水平低于对照组(P值均<0.05)。而术后72 h实验组、对照组血清ALT、AST水平均低于术后24 h(ALT:t=8.87、7.92;AST:t=5.04、5.34,P值均<0.05)。术后24 h和72 h实验组ULK1、LC3 mRNA水平、蛋白水平较假手术组升高(P值均<0.05),24 h实验组ULK1 mRNA水平(13.23±6.58 vs 4.91±1.64)、LC3 mRNA水平(7.82±1.65 vs 3.70±1.10)、ULK1蛋白水平(1.62±0.19 vs 1.17±0.33)、LC3蛋白水平(1.62±0.19 vs 0.84±0.10)较对照组增加(P值均<0.05); 72 h实验组ULK1 mRNA水平(10.58±3.31 vs 4.83±2.66)、LC3 mRNA水平(6.42±1.13 vs 2.71±0.81)、ULK1蛋白水平(1.29±0.24 vs 0.90±0.29)、LC3蛋白水平(1.40±0.73 vs 0.64±0.08)较对照组增加(P值均<0.05)。肝脏缺血再灌注损伤72 h后实验组、对照组血清ALT、AST水平较术后24 h降低,并且肝脏病理结构损伤减轻,ULK1、LC3 mRNA水平、蛋白水平降低(P值均<0.05)。结论 肝脏缺血再灌注损伤后ULK1、LC3表达增加,雷帕霉素可能在肝脏缺血再灌注损伤过程中通过上调细胞自噬保护肝脏功能。
【Abstract】: Objective To investigate the effect of rapamycin on the expression of the autophagy-related proteins Unc-51 like autophagy activating kinase 1 (ULK1) and microtubule-associated protein 1 light chain 3 (LC3) in hepatic ischemia-reperfusion injury and its significance. Methods A total of 30 rats were divided into experimental group, control group, and sham-operation group, with 10 rats in each group, and a rat model of hepatic ischemia-reperfusion injury was established. Samples were collected at 24 and 72 hours after surgery, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver pathology, and mRNA and protein expression of ULK1 and LC3 were measured. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results There were increases in the serum levels of ALT and AST and liver pathological structural damage at 24 hours after surgery (F=1531.83 and 1799.97, P<0.05), and compared with the control group, the experimental group had significant reductions in the serum levels of ALT (354.58±28.40 U/L vs 556.15±19.32 U/L, P<0.05) and AST (384.37±8.98 U/L vs 575.96±30.21 U/L, P<0.05) and alleviation of liver pathological structural damage. At 72 hours after surgery, the experimental group had significantly lower serum levels of ALT and AST than the control group (ALT: 271.81±8.63 U/L vs 466.33±30.00 U/L, P<0.05; AST: 358.92±13.20 U/L vs 497.05±40.14 U/L, P<0.05). Both the experimental group and the control group had significant reductions in the serum levels of ALT and AST from 24 to 72 hours after surgery (ALT:t=8.87、7.92,AST:t=5.04、5.34, both P<0.05). At 24 hours after surgery, the experimental group and the control group had significant increases in the mRNA and protein expression of ULK1 and LC3 compared with the sham-operation group (all P<0.05), and compared with the control group, the rapamycin intervention group had significant increases in the mRNA and protein expression of ULK1 and LC3 (ULK1 mRNA: 13.23±6.58 vs 4.91±1.64, P<0.05; LC3 mRNA: 7.82±1.65 vs 3.70±1.10, P<0.05; ULK1 protein: 1.62±0.19 vs 1.17±0.33, P<0.05; LC3 protein: 1.62±0.19 vs 0.84±0.10, P<0.05). Compared with the control group at 72 hours after surgery, the rapamycin intervention group had significant increases in the mRNA and protein expression of ULK1 and LC3 (ULK1 mRNA: 10.58±3.31 vs 4.83±2.66, P<0.05; LC3 mRNA: 6.42±1.13 vs 2.71±0.81, P<0.05; ULK1 protein: 1.29±0.24 vs 0.90±0.29, P<0.05; LC3 protein: 1.40±0.73 vs 0.64±0.08, P<0.05). There were significant reductions in the serum levels of ALT and AST from 24 to 72 hours after hepatic ischemia-reperfusion injury, with alleviation of liver pathological structural damage and reductions in the mRNA and protein expression of ULK1 and LC3 (all P<0.05). Conclusion There are increases in the expression of ULK1 and LC3 after hepatic ischemia-reperfusion injury, and rapamycin may exert a protective effect on liver function by upregulating autophagy during liver ischemia-reperfusion injury.
【关键字】:再灌注损伤; 自噬相关同源蛋白1; 微管相关蛋白1轻链3; 西罗莫司; 大鼠, Sprague-Dawley
【Key words】:reperfusion injury; autophagy-related protein-1 homolog; microtubule associated protein 1 light chain 3; sirolimus; rats, Sprague-Dawley
【引证本文】:YANG LC, ZHANG XY, PAN NB, et al. Effect of rapamycin on the expression of autophagy-related proteins Unc-51 like autophagy activating kinase 1 and microtubule-associated protein 1 light chain 3 in hepatic ischemia-reperfusion injury and its significance[J]. J Clin Hepatol, 2019, 35(10): 2261-2265. (in Chinese)
杨龙灿, 张旭阳, 潘宁波, 等. 雷帕霉素在肝脏缺血再灌注损伤中对自噬相关蛋白ULK1、LC3表达的影响[J]. 临床肝胆病杂志, 2019, 35(10): 2261-2265.

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