Effect Of ω-3Polyunsaturated Fatty Acids (ω-3PUFA) On Liver Regeneration After90%Partial Hepatectomy (PH) In Rats

Objective To observe the effect of ω-3polyunsaturated fatty acids (ω-3PUFA) on protection of liver function and liver regeneration after90%hepatectomy in rats.Methods Fifty four male SD rats were randomly divided into sham group,control group (90%hepatectomy),study group(90%hepatectomy+2ml/kg ω-3PUFA intravenous injection). The survival rate was observed and liver function was checked at12h,18h,24h after90%hepatectomy.Proliferation of hepatocytes were assesseed by immunostaining technique and the morphology of liver tissue was observed via HE staining and transmission electron microscope. The levels of inflammatory cytokines such as IL-4,IL-10,IL-6and TNF-a in serum were determined by ELISA, and the expressions of Akt, GSK3β,.STAT3were investigated by Western Blotting. All data are shown as the mean±tandard(x±s) deviation.T-test was used for the comparison between two groups and Kaplan-Meier estimator was used for the survival rate evaluation.Results (1) Compared to control group,the survival rate was increased significantly in study group(P=0.001).(2) Compared to control group, the levels of total protein and albumin in peripheral blood were increased significantly in study group at12h,18h and24h after90%hepatectomy, differences between groups were considered statistically significant when P<0.05(TP t12h=2.576, P12h=0.042; t18h=2.271, P18h=0.047; t24h=3.037, P24h=0.032; Alb t12h=3.420, P12h=0.001; t18h=2.749, P18h=0.021; t24h=4.133,P24h=0.013); The level of alanine transaminase and aspartate aminotransferase was decreased significantly in study group at24h after90%hepatectomy, differences between groups were considered statistically significant when P<0.05(ALT t24h=3.894,P24h=0.039; AST t24h=2.675,P24h=0.031);The level of alkaline phosphatase was decreased significantly in study group at12h after90%hepatectomy,differences between groups were considered statistically significant when P<0.05(t=2.838, P=0.001)(3)Compared to the control group, the liver weight/body weight ratios was increased significantly in study group at18h and24h after90%hepatectomy, differences between groups were considered statistically significant when P<0.05(t18h=4.128, P18h=0.001; t24h=5.019, P24h=0.001); Immunohistochemistry showed that the number of ki67positive cells was increased significantly in study group at24h after90%hepatectomy, differences between groups were considered statistically significant when P<0.05(t=16.146, P=0.001)(4) HE staining and transmission electron microscopy showed that hepatocyte swelling and ballooning degeneration of liver cells were more obvious in the control group at all time points, In contrast, in the study group, no obvious hepatocyte swelling and ballooning degeneration was observed at12h after90%hepatectomy, hepatocellular apoptosis was decreased significantly at18h after90%hepatectomy, The liver cell restores normally, the hepatic lobe structure is clear at24h after90%hepatectomy.(5) Compared to control group, anti-inflammatory cytokines including IL-4, IL-10were increased significantly in study group at18h、24h after90%hepatectomy, differences between groups were considered statistically significant when P<0.05(IL-4t18h=25.87, P18h=0.002;t24h=37.23, P24h=0.001;IL-10t18h=7.87,P18h=0.016; t24h=20.14, P24h=0.003); pro-inflammation cytokines IL-6was decreased significantly in study group at12h、18h after90%hepatectomy, pro-inflammation cytokines TNF-a was decreased significantly in study group at24h after90%hepatectomy differences between groups were considered statistically significant when P<0.05(IL-6t12h=25.87, P12h=0.002; t18h=10.127, P18h=0.001; TNF-a t24h=6.73, P24h=0.013).(6) Compared to control group, Akt was phosphorylated in the samples of12h after90%hepatectomy and phosphorylated Akt was increased in the samples of18h after90%hepatectomy. In addition, GSK3β was phosphorylated at12h after90%hepatectomy, the phosphorylation level of GSK3β is higher. Moreover, the expression of phosphorylated STAT3was much higher and sustained longer in the study group at12,18and24h after90%hepatectomy. Conclusion ω-3polyunsaturated fatty acids can significantly improve survival rates, protect the residual liver function, reduce the release of pro-inflammatory cytokines, increase anti-inflammatory cytokine release and significantly promote liver regeneration.This study provides a valuable theoretical and experimental basis for the application of ω-3polyunsaturated fatty acids in perioperative period of extensive liver resection...