Berberine protects against kidney ischemia/reperfusion injury caused by autologous orthotopic liver transplantation in rats via activate Akt pathway
(1.Department of Anesthesiology, The First Center Clinic College, Tianjin Medical University,Tianjin 300192,China; 2. Department of Anesthesiology, Tianjin First Center Hospital,Tianjin 300192, China; 3.The Key Laboratory of Critical Care of Medicine Ministry of Health,Tianjin 300384, China)
Objective: To explore the protective effects of berberine against kidney damage caused by autologous orthotopic liver transplantation(OLAT). Methods:Sprague-Dawley rats were randomly divided into three groups(n=8): (1)sham group(S group);(2)autotransplantation(AT group);(3)autotransplantation plus BBR group(BBR group). In S groups,rats were anesthetized and simply freed the blood vessels and ligaments.In AT groups,rats underwent autologous orthotopic liver transplantation. In BBR groups, berberine was administered intragastricly 200 mg/(kg·day) for 7 days before autotransplantation. Eight hours after surgery, the rats were killed and the kidneys were harvested for determination of BUN, Cr,histologic injury,superoxide dismutase(SOD),Malondialdehyde(MDA),the protein expression levels of p-Akt and the count of cell apoptosis. Results: MDA,BUN, Cr , protein expression levels of p-Akt and the count of cell apoptosis were significantly higher in the AT and BBR groups than in the S group.These indicators including MDA, BUN,Cr and the count of cell apoptosis was significantly higher in the AT group than in the BBR group. In the BBR group, protein expression levels of p-Akt were higher than those in the AT group.The levels of SOD were significantly lower in the AT group and BBR group than in the S group.The levels of SOD in the BBR group were)greatly higher than in the AT group. Light microscopy demonstrated that histological tissue damage greatly reduced in the BBR as compared to the AT group,while no injury was discovered in the sham group. Conclusion:Berberine can protect against kidney ischemical/reperfusion injury during autotransplantation in rats.
[1]Matsui T, Rosenzweig A. Convergent signal transduction pathways controlling cardiomyocyte survival and function:the role of PI3-kinase and Akt[J]. J Mol Cell Cardiol, 2005, 38(1): 63[2]Andreucci M, Michael A, Kramers C, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1[J]. Kidney Int, 2003, 64(4): 1189
[3]张日东,白瑞苗,魏敬.盐酸小檗碱对大鼠肾小管上皮细胞缺血再灌注损伤的保护作用[J].中国实验方剂学杂志,2011,17(4):165
[4]Yu W l Sheng M, Xu R B, et al. Berberine protects human renal proximal tubular cells from hypoxia/reoxygenation injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways[J]. J Transl Med, 2013, 11: 24
[5]Nozato E, Shiraishi M, Miyaguni T, et al. In situ perfusion of the liver under portosystemic shunt in rats:a stable model of cold ischemia for orthotopic liver transplantation[J]. Transplant Proc, 1998, 30(7): 3718
[6]Bopassa J C, Ferrera R, Gateau-Roesch O, et al. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning[J]. Cardiovasc Res, 2006, 69(1): 178
[7]Devarajan P. Update on mechanisms of ischemic acute kidney injury[J]. J Am Soc Nephrol, 2006, 17(6): 1503
[8]Mullonkal C J, Toledo-Pereyra L H. Akt in ischemia and reperfusion[J]. J Invest Surg, 2007, 20(3): 195
[9]Yuan X, Jing S B, Wu L Z, et al. Pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury in rats by activating the phosphatidylinositol 3-kinase pathway[J]. Exp Ther Med, 2014, 8(3): 973
[10]Zhang R, Zhang L, Manaenko A, et al. Helium preconditioning protects mouse liver against?ischemia?and?reperfusion injury?through the PI3K/Akt pathway[J]. J Hepatol, 2014, 61(5): 1048
[11]Liang K, Ye Y, Wang Y, et al. Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway[J]. J Neurol Sci, 2014, 344(1/2): 100
[12]Chen S D, Chen Y B, Peng Y, et al. Role of PI3K/Akt signaling in the protective effect of Magnesium sulfate against ischemia-perfusion injury of small intestine in rats[J]. Chin Med J (Engl), 2010, 123(11): 1447
通信作者:杜洪印, E-mail:duhongyin@medmail.com.cn。