Galectin-3在CCl_4致肝损伤及对GRP78调控的作用

Role of galectin-3 in CCl_4-induced hepatic damage and in modulation of GRP78 in mice

目的:探讨Galectin-3对CCl_4致急性肝损伤时GRP78的调控作用.方法:选择ICR系的♂Galectin-3基因敲除型[Gal-3(-/-)]和其野生型[Gal(+/+)1小鼠,一次灌胃给予CCl_4,观察给药后10,24,48和72 h的肝组织病理改变和检测其血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性,并检测肝细胞不同细胞组分中的GRP78蛋白表达.结果:与Gal(+/+)型鼠比较,CCl_4对Gal-3(-/-)型鼠的肝组织病理损伤出现时间早、损伤程度重.Gal-3(-/-)型鼠在CCl_4灌胃后10和24 h的血清ALT活性(1 860±191 U/L vs 1356±177 U/L,t=6.12,P<0.01;2789±236 U/L vs 2468±221 U/L,f=3.14,P<0.01)及CCl_4灌胃后10 h的血清AST活性(946±89 vs 623±73 U/L,t=8.87,P<0.01)与Gal(+/+)型鼠比较显著升高.对照组中Gal-3(+/+)型鼠的微粒体组分(Mic)中的GRP78蛋白表达显著高于Gal-3(-/-)型鼠(140.9±21.1 vs 76.1±9.5,t=8.86,P<0.01).在CCl_4 ig后24 h,Gal-3(+/+)型鼠的肝细胞线粒体组分(Mt)和Mic中的GRP78蛋白表达明显升高,并显著高于Gal-3(-/-)型鼠(Mt:127.0±18.8 vs 49.1±6.3,P<0.01;Mic:166.5±23.4 vs 87.7±11.6,P<0.01).结论:Galectin-3蛋白在CCl_4致急性肝损伤中可能具有一定的保护作用.上调Mic和Mt中的GRP78蛋白表达可能是Galectin-3在CCl_4对肝细胞损伤中发挥保护作用的一个途径.

AIM： To evaluate the role of galectin-3 in CC14- induced liver damage and in modulation of Glucose regulated protein 78 （GRP78） in mice. METHODS： Ten-week-old, Gal-3 （-/-） and Gal-3 （＋/＋） ICR male mice were treated with CCl4 （8 mL/kg） by lavage. Mice were killed at 0, 10, 24, 48 and 72 h after CC14 administration. Pathological changes in the liver, serum activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）, and expression of GRP78 protein in different parts of the liver were examined. RESULTS： Pathological changes induced by CC14 in the liver of Gal-3 （-/-） mice were earlier and more serious than those in Gal-3 （＋/＋） mice. Serum activity of ALT in Gal-3 （-/-） mice was higher than that in Gal-3 （＋/＋） mice at 10 and 24 h after treatment with CCl4 （1860 ± 191 U/L vs 1356 ± 177 U/L, t = 6.12, P 〈 0.01; 2789 ± 236 U/L vs 2468 ± 221 U/L, t = 3.14, P 〈 0.01）. In the control experiment, the expression of GRP78 protein in the Mic part of the liver cells of Gal-3 （＋/＋） mice was higher than that in Gal-3 （-/-） mice （140.9 ± 21.1 vs 76.1 ± 9.5, t = 8.86, P 〈 0.01）. Twenty-four hours after CCl4 administration, the expression of GRP78 protein in both the Mt and Mic parts of the liver cells of Gal-3 （＋/＋） mice was significantly up-regulated, compared with that in Gal-3 （-/-） mice （Mt, 127.0 ± 18.8 vs 49.1 ± 6.3, P 〈 0.01; Mic, 166.5 ± 23.4 vs 87.7 ± 11.6, P 〈 0.01）. CONCLUSION： Galectin-3 seems to protect mouse liver from CCl4-induced damage, which may be attributed to the up-regulation of GRP78 protein.