ω-3多不饱和脂肪酸对大鼠肝切除术后肝脏紧密连接及肝再生的影响

Effect of ω-3 polyunsaturated fatty acids on hepatic tight junctions and liver regeneration in rats after partial hepatectomy

目的:探讨ω-3多不饱和脂肪酸(ω-3PUFA)对大鼠肝切除术后肝脏紧密连接和肝脏再生的影响.方法:采用大鼠70%肝切除模型,♂SD大鼠80只随机分为假手术组、70%肝切除对照组、小剂量ω-3PUFA组(1mL/kg)和大剂量ω-3PUFA组(2mL/kg).检测术后1、2、3、5d血清总胆汁酸、总胆红素、ALT和白蛋白值.Western blot检测肝脏紧密连接蛋白Occludin,Claudin-3和ZO-1表达及反映肝再生的PCNA表达.激光共聚焦显微镜下观察肝脏紧密连接结构变化.结果:术后1d,与对照组相比较,ω-3PUFA组血清总胆汁酸(181.2±63.9,166.7±68.9vs228.9±37.7),总胆红素(13.5±8.8,7.6±0.1vs25.9±15.3)和ALT(1042.2±179.7,901.4±182.3vs2703.9±130.0)均显著降低(P<0.05),白蛋白(27.2±1.1,29.8±0.9vs30.5±1.2)无明显变化.术后2d,与对照组相比较,ω-3PUFA组血清总胆红素(6.8±9.2,6.1±2.0vs17.7±1.1)和ALT(452.8±258.5,499.8±155.9vs1466.5±30.2)均显著降低(P<0.05),白蛋白(26.8±0.4,27.7±1.0vs25.7±0.6)无明显变化.ω-3PUFA组术后1、2、5d肝脏紧密连接(Occludin,Claudin-3,ZO-1)的表达显著增加(P<0.05),术后1、2、3、5d肝脏再生程度明显增加(P<0.05).激光共聚焦显示ω-3PUFA组肝脏紧密连接结构恢复.结论:ω-3PUFA可以促进大鼠肝切除术后肝脏紧密连接的稳定高表达,保护其结构,并促进肝再生,保护肝功能.

AIM：To investigate the effect of ω-3 polyunsaturated fatty acids（PUFAs） on hepatic tight junctions and liver regeneration in rats after partial hepatectomy（PH） METHODS：A rat model of 70% PH was used in this study.Eighty male SD rats were randomly divided into sham operation group,PH group,PH ＋ low-dose ω-3 PUFA（1 mL/kg） group and PH ＋ high-dose ω-3 PUFA（2 mL/kg） group.Serum samples were collected to measure thelevels of total bile acids,total bilirubin,alanine aminotransferase（ALT） and albumin on days 1,2,3 and 5 after PH.Tissue samples were collected for detecting the expression of hepatic tight junction proteins（Occludin,Claudin-3 and 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.RESULTS：In comparison with the PH group on day 1,the levels of total bile acids（181.2 ± 63.9,166.7 ± 68.9 vs 228.9 ± 37.7）,total bilirubin（13.5 ± 8.8,7.6 ± 0.1 vs 25.9 ± 15.3） and ALT（1042.2 ± 179.7,901.4 ± 182.3 vs 2703.9 ± 130.0） decreased significantly in the low-and highdose ω-3 PUFA groups（all P 0.05）,whereas no marked changes in the level of albumin（27.2 ± 1.1,29.8 ± 0.9 vs 30.5 ± 1.2） were observed.Compared to the PH group on day 2,a significant decrease in the levels of total bilirubin（6.8 ± 9.2,6.1 ± 2.0 vs 17.7 ± 1.1） and ALT（452.8 ± 258.5,499.8 ± 155.9 vs 1 466.5 ± 30.2） was noted in the low-and high-dose ω-3 PUFA groups（all P 0.05）,whereas no marked changes in the level of albumin（26.8 ± 0.4,27.7 ± 1.0 vs 25.7 ± 0.6） were observed.The expression of hepatic tight junction proteins（Occludin,Claudin-3 and ZO-1） increased significantly on days 1,2 and 5 after PH（all P 0.05）,and liver regeneration was enhanced significantly on days 1,2,3 and 5 after PH（all P 0.05）.Treatment with ω-3 PUFAs promoted structural restoration of hepatic tight junctions.CONCLUSION：ω-3 PUFAs 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.