1,25-二羟基维生素D_3对小鼠非酒精性脂肪肝性肝纤维化进程的抑制作用  

1,25-dihydroxyvitamin D_3 inhibits fibrosis in mice with NAFLD induced by a methionine-choline-deficient diet

作　　者：李艳芳[1] 唐夕岚[1] 凌文华[1] 

机构地区：[1]中山大学公共卫生学院营养系,广东省广州市510080

出　　处：《世界华人消化杂志》2012年第33期3191-3196,共6页World Chinese Journal of Digestology

基　　金：国家重点基础研究发展计划(973计划)基金资助项目;No.2012CB517506~~

摘　　要：目的:探讨1,25-二羟基维生素D3[1,25-dihydroxyvitamin D3,1,25(OH)2D3]对蛋氨酸-胆碱缺乏(methionine-choline-deficient,MCD)饮食诱导的非酒精性脂肪肝性肝纤维化的抑制作用及其可能机制.方法:将30只C57BL/6J小鼠随机分为正常组、模型组和干预组,每组10只.采用MCD饮食诱导建立非酒精性脂肪肝性肝纤维化模型.其中,模型组和干预组饲以MCD饲料.干预组给予1,25(OH)2D3(5μg/kg)腹腔注射,正常组和模型组给予同样剂量的生理盐水腹腔注射,2次/wk.干预8wk后,试剂盒检测小鼠血清谷丙转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate aminotransferase,AST)水平;肝组织苏木素和伊红(hematoxylin and eosin,HE)染色观察组织形态学变化;RT-PCR检测转化生长因子β(transforming growth factor beta,TGF-β)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和Ⅰ型胶原mRNA的表达.结果:与正常组相比,模型组小鼠ALT和AST水平以及TGF-1,α-SMA和Ⅰ型胶原mRNA的表达均明显升高(P=0.000,P=0.000,P=0.044,P=0.003,P=0.027);而与模型组相比,1,25(OH)2D3干预组除了TGF-β1mRNA的表达无变化外,其他指标均显著下降(P=0.000,P=0.005,P=0.020,P=0.027).HE染色结果显示,模型组肝组织可见大量脂肪变性(胞质内充满大小较一致的脂滴空泡),且血管周围炎症细胞浸润严重;而干预组两者程度都有减轻,但后者效果更明显.结论:1,25(OH)2D3可改善肝功能,且可能通过对-SMA和Ⅰ型胶原基因的调控达到减缓MCD饮食诱导的非酒精性脂肪肝性肝纤维化进程的目的.AIM:To investigate whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, inhibits fibrosis induced by a methionine-choline-defficient (MCD) diet in C57BL/6J mice and to explore the possible mechanisms involved. METHODS:Male C57BL/6J mice (n = 30) were divided randomly into control group, MCD group, and MCD + 1,25(OH)2D3 group. The MCD and MCD + 1,25(OH)2D3 groups were fed a MCD diet. All the mice were intraperitoneally injected with 1,25(OH)2D3 (5 μg/kg) or equal volume of saline twice weekly. After 8 wk, the mice were sacrificed to take serum samples for biochemical measurements and liver samples for HE staining and RT-PCR. RESULTS:Serum levels of alanine aminotransferase, aspartate aminotransferase, and mRNA expression of transforming growth factor beta1 (TGF-β1), α-smooth muscle actin (α-SMA) and collagenⅠa1 of MCD group significantly increased in the MCD group compared to the control group (P = 0.000, 0.000, 0.044, 0.003, 0.027). In the MCD + 1,25(OH)2D3 group, all the above parameters significantly decreased (P = 0.000, 0.005, 0.020, 0.027) except the mRNA expression of TGF-β1, which showed no significant change, compared to the MCD group. Steatosis was significantly improved, as revealed by the presence of fewer lipid drops in the cytoplasm and less inflammatory cell infiltration around the vessels, in the MCD + 1,25(OH)2D3 group compared to the MCD group. CONCLUSION:1,25(OH)2D3 can improve liver function and inhibit fibrosis possibly by down-regulating the mRNA expression of α-SMA and collagenⅠa1 in mice with NAFLD induced by a MCD diet.

关 键 词：1 25-二羟基维生素D3 蛋氨酸-胆碱缺乏 肝纤维化 转化生长因子Β Α-平滑肌肌动蛋白 Ⅰ型胶原 

分 类 号：R575.5[医药卫生—消化系统]