Effects Of N-3Polyunsaturated Fatty Acids On Hepatic Tight Junctions And Liver Regeneration After Partial Hepatectomy In Rat

Objective:To investigate the effect of ω-3polyunsaturated fatty acids (PUFAs) on hepatic tight junctions and liver regeneration in rats after partial hepatectomy (PH) and explore the possible mechanism.Methods:A rat model of70%PH was used in this study. Eighty male SD rats were randomly divided into sham operation group, PH group, PH+low-dose ω-3PUFA (1mL/kg) group and PH+high-dose ω-3PUFA (2mL/kg) group. Serum samples were collected to measure the levels of total bile acids, total bilirubin, alanine aminotransferase (ALT) and albumin on days1,2,3and5after PH. Tissue samples were collected for detecting the expression of hepatic tight junction proteins (Occludin, Claudin-3and ZO-1) and PCNA (a parameter reflecting liver regeneration) by Western blot. Tissue samples were also collected for observation of structural changes in hepatic tight junctions by confocal microscopy. LKB1-AMPK signaling pathway, the possible mechanism, was also examined using Western Blot.Results:In comparison with the PH group on day1, the levels of total bile acids, total bilirubin and ALT decreased significantly in the low-and high-dose ω-3PUFA groups (all P< 0.05). whereas no marked changes in the level of albumin were observed. Compared to the PH group on day2. a significant decrease in the levels of total bilirubin and ALT was noted in the low-and high-dose ω-3PUFA groups (all P<0.05), whereas no marked changes in the level of albumin were observed. The expression of hepatic tight junction proteins (Occludin, Claudin-3and ZO-1) increased significantly on days1,2and5after PH (all P<0.05). and liver regeneration was enhanced significantly on days1,2,3and5after PH (all P<0.05). Confocal microscopy of hepatic TJs revealed that in the low-and high-dose ω-3PUFA groups on day3after PH, the intensity of Occludin, Claudin-3and ZO-1staining were enhanced and these hepatic TJs were present as continuous lines and demonstrated reduced disorder compared to PH group. Compared to the PH group, the expression of phos-LKB1and phos-AMPK increased significantly on days1.2and5in the low-and high-dose ω-3PUFA groups (all P<0.05).Conclusions:ω-3PUFAs not only promote the expression of tight junction proteins and protect the structure of hepatic tight junctions. but also promote liver regeneration and protect liver function in rats after PH. which may be attributed to the activation of LKB1-AMPK signaling pathway.