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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 10
Oct.  2019
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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

DOI: 10.3969/j.issn.1001-5256.2019.10.026
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  • Received Date: 2019-03-27
  • Published Date: 2019-10-20
  • 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.

     

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