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Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation.
Transplant Proc. 2017 Oct; 49(8):1923-1929.TP

Abstract

BACKGROUND

To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro.

METHODS

Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K+, Na+, Cl-, blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods. Renal cortex were harvested at 6 hours for the following measurement: lactic acid (LD), adenosine triphosphate (ATP), malondialdehyde (MDA), neutrophil accumulation (MPO), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β). Ischemia-induced apoptosis and the protein expression levels of total Akt, phospho-Akt, total Erk, and phospho-Erk were analyzed by Western blotting.

RESULTS

Almost all of the tested metabolites in preservation solutions were reduced with time in the HMP group. Levels of Na+, Cl-, BUN, Cr, K+, and LDH were lower in the HMP group compared with the SCS group, with differences in the first 4 reaching statistical significance. HMP alleviated ATP degradation and LD accumulation, diminished the MDA (P < .05) and MPO (P = .227) levels, and greatly raised IL-10 and TGF-β (P < .05) expression. A marked decrease of proapoptotic and a large increase of antiapoptotic markers (P < .05) along with greatly raised Akt (P < .05) and Erk (P < .01) phosphorylation was observed in the kidney of the HMP group compared with the SCS group.

CONCLUSION

HMP's kidney graft protection involves inhibition of accumulation of toxic metabolites, oxidative damage, and apoptosis along with upregulation of the Akt and Erk signaling pathway.

Authors+Show Affiliations

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, China.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, China. Electronic address: linzhou19@163.com.Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, China. Electronic address: shusenzheng@zju.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28923649

Citation

He, N, et al. "Hypothermic Machine Perfusion's Protection On Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation." Transplantation Proceedings, vol. 49, no. 8, 2017, pp. 1923-1929.
He N, Li JH, Jia JJ, et al. Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation. Transplant Proc. 2017;49(8):1923-1929.
He, N., Li, J. H., Jia, J. J., Xu, K. D., Zhou, Y. F., Jiang, L., Lu, H. H., Yin, S. Y., Xie, H. Y., Zhou, L., & Zheng, S. S. (2017). Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation. Transplantation Proceedings, 49(8), 1923-1929. https://doi.org/10.1016/j.transproceed.2017.05.011
He N, et al. Hypothermic Machine Perfusion's Protection On Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation. Transplant Proc. 2017;49(8):1923-1929. PubMed PMID: 28923649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation. AU - He,N, AU - Li,J-H, AU - Jia,J-J, AU - Xu,K-D, AU - Zhou,Y-F, AU - Jiang,L, AU - Lu,H-H, AU - Yin,S-Y, AU - Xie,H-Y, AU - Zhou,L, AU - Zheng,S-S, PY - 2017/03/17/received PY - 2017/04/29/revised PY - 2017/05/13/accepted PY - 2017/9/20/entrez PY - 2017/9/20/pubmed PY - 2018/5/16/medline SP - 1923 EP - 1929 JF - Transplantation proceedings JO - Transplant Proc VL - 49 IS - 8 N2 - BACKGROUND: To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro. METHODS: Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K+, Na+, Cl-, blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods. Renal cortex were harvested at 6 hours for the following measurement: lactic acid (LD), adenosine triphosphate (ATP), malondialdehyde (MDA), neutrophil accumulation (MPO), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β). Ischemia-induced apoptosis and the protein expression levels of total Akt, phospho-Akt, total Erk, and phospho-Erk were analyzed by Western blotting. RESULTS: Almost all of the tested metabolites in preservation solutions were reduced with time in the HMP group. Levels of Na+, Cl-, BUN, Cr, K+, and LDH were lower in the HMP group compared with the SCS group, with differences in the first 4 reaching statistical significance. HMP alleviated ATP degradation and LD accumulation, diminished the MDA (P < .05) and MPO (P = .227) levels, and greatly raised IL-10 and TGF-β (P < .05) expression. A marked decrease of proapoptotic and a large increase of antiapoptotic markers (P < .05) along with greatly raised Akt (P < .05) and Erk (P < .01) phosphorylation was observed in the kidney of the HMP group compared with the SCS group. CONCLUSION: HMP's kidney graft protection involves inhibition of accumulation of toxic metabolites, oxidative damage, and apoptosis along with upregulation of the Akt and Erk signaling pathway. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/28923649/Hypothermic_Machine_Perfusion's_Protection_on_Porcine_Kidney_Graft_Uncovers_Greater_Akt_Erk_Phosphorylation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(17)30553-5 DB - PRIME DP - Unbound Medicine ER -