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

杨龙灿; 张旭阳; 潘宁波; 余曦; 李继维; 张莹

doi:10.3969/j.issn.1001-5256.2019.10.026

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

DOI: 10.3969/j.issn.1001-5256.2019.10.026

1. 铜仁市人民医院肝胆外科
2. 遵义医科大学
3. 贵州省人民医院肝胆外科
4. 毕节市第一人民医院普外科

基金项目:

贵州省留学人员科技创新项目[黔人项目资助合同(2016)21号]；贵州省科技计划项目[黔科基础2016(1088)]；贵州省卫生计生委科学技术基金(gzwjkj2018-1-046)；

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中图分类号: R575
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出版历程
- 收稿日期: 2019-03-27
- 出版日期: 2019-10-20

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

Department of Hepatobiliary Surgery,Tongren People's Hospital

Research funding:

摘要

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...
- 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
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.
- reperfusion injury /
- autophagy-related protein-1 homolog /
- microtubule associated protein 1 light chain 3 /
- sirolimus /
- rats,Sprague-Dawley

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参考文献(15)

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