Effect of sorafenib on liver regeneration after partial hepatoectomy in liver cirrhotic rats
Zhou Xiao
Abstract
Zhou Xiao
Abstract
AIM:To study the effect of sorafenib on the liver regeneration after partial hepatectomy(PH) in cirrhotic rats.METHODS;Thirty Wistar rats with liver cirrhosis induced successfully with diethylnitrosamine(DEN) underwent 30%PH and then were randomly divided into 2 groups(re = 15).The rats in experimental group were fed with sorafenib at dose of 30 mg ? kg~(-1) ? d~(-1) from the 1st day to the 10th day after PH,while those in control group were fed with vehicle by gavage.The blood and liver tissues of the rats were collected after PH and at the end of the experiment. Liver regeneration rate(LRR) and proliferating cell nuclear antigen(PCNA) expression were assessed for determining the hepatocyte proliferation.The content of alanine transaminase(ALT),albumin(ALB),total bilirubin(TBIL),direct bilirubin (DBIL),angiogenesis related factors including vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR-2 ),platelet-derived growth factor receptorβ(PDGFR -β) and micro-vessel density(MVD) were measured in both groups.RESULTS;LRRs on day 10 after PH were 45.43%±3.36%and 44.21%±2.77%in experimental group and control group,respectively(P 0.05),and the expression of PCNA in hepatic tissues of the rats was not found by the method of immunohistochemistry in both groups.Liver function index had no significant difference between the 2 groups(P 0.05 ).However,other than VEGF,sorafenib resulted in inhibition of VEGFR-2 and PDGFR -βexpression and reduction of MVD in experiment group,and significant difference between the 2 groups was observed(P 0.01 ). CONCLUSION:Sorafenib does not influence live regeneration after PH in liver cirrhotic rats.
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AIM:To study the effect of sorafenib on the liver regeneration after partial hepatectomy(PH) in cirrhotic rats.METHODS;Thirty Wistar rats with liver cirrhosis induced successfully with diethylnitrosamine(DEN) underwent 30%PH and then were randomly divided into 2 groups(re = 15).The rats in experimental group were fed with sorafenib at dose of 30 mg ? kg~(-1) ? d~(-1) from the 1st day to the 10th day after PH,while those in control group were fed with vehicle by gavage.The blood and liver tissues of the rats were collected after PH and at the end of the experiment. Liver regeneration rate(LRR) and proliferating cell nuclear antigen(PCNA) expression were assessed for determining the hepatocyte proliferation.The content of alanine transaminase(ALT),albumin(ALB),total bilirubin(TBIL),direct bilirubin (DBIL),angiogenesis related factors including vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR-2 ),platelet-derived growth factor receptorβ(PDGFR -β) and micro-vessel density(MVD) were measured in both groups.RESULTS;LRRs on day 10 after PH were 45.43%±3.36%and 44.21%±2.77%in experimental group and control group,respectively(P 0.05),and the expression of PCNA in hepatic tissues of the rats was not found by the method of immunohistochemistry in both groups.Liver function index had no significant difference between the 2 groups(P 0.05 ).However,other than VEGF,sorafenib resulted in inhibition of VEGFR-2 and PDGFR -βexpression and reduction of MVD in experiment group,and significant difference between the 2 groups was observed(P 0.01 ). CONCLUSION:Sorafenib does not influence live regeneration after PH in liver cirrhotic rats.
Key concepts: Liver regeneration, Proliferating cell nuclear antigen, Internal medicine, Vascular endothelial growth factor, Angiogenesis, Liver function, Sorafenib, Endocrinology