全反式维甲酸对慢性酒精性肝损伤大鼠肝脏TGF-β1、CTGF和Col1a1表达的影响  

Effect of all-trans retinoic acid on expression of TGF-β1, CTGF and Col1a1 in chronic alcoholic liver disease in rats

作　　者：付妤[1] 但自力[1] 唐望先[2] 晏维[2] 潘志红[1] 熊章鄂[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院消化内科,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院肝病研究所,湖北省武汉市430030

出　　处：《世界华人消化杂志》2006年第2期179-183,共5页World Chinese Journal of Digestology

摘　　要：目的:通过观察全反式维甲酸对慢性酒精性肝损伤大鼠肝脏TGF-β1、CTGF和Collal表达的影响,探讨该药物对酒精性肝纤维化形成的作用．方法:大鼠24只随机分为3组:酒精组(J组),给予酒精-玉米油混悬液灌胃;治疗组(A组),给予上述混悬液灌胃8 wk后加用0,15 mg／(kg·d) 的全反式维甲酸灌胃;对照组(N组),给予等量的生理盐水和玉米油灌胃．16 wk后处死大鼠．光、电镜下观察肝组织病理改变,高压液相色谱法(HPLC)测肝组织中维甲酸的含量,免疫组化法检测肝组织中转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)的蛋白水平,逆转录聚合酶链反应(RT-PCR)检测肝组织中TGF-β1、CTGF和Ⅰ型胶原前胶原α1(Collal)的mRNA水平．结果:光镜下酒精组及治疗组均呈不同程度的酒精性肝炎改变,电镜下酒精组肝细胞线粒体肿胀,内质网扩张,脱颗粒,而治疗组改变轻于酒精组．肝组织中维甲酸含量:酒精组低于正常组,治疗组接近对照组水平．Collal 的mRNA表达在酒精组中较对照组明显增高 (0．18±0．03 vs 0．10±0．02,P<0．01),治疗组较酒精组表达下降(0．14±0．03 vs 0．18±0．03,P <0．05)．TGF-β1的mRNA及蛋白表达在酒精组中增高(0．53±0．17 vs 0．34±0．05,105．93 ±10．12 vs 149．27±10．17,P<0．01),治疗组相对于酒精组有所下降(0．41±0．06 vs 0．53± 0．17,130．80±6.23 vs 105．93±10．12,P<0．05)． CTGF的mRNA及蛋白表达在酒精组中增高 (0．41±0．13 vs 0．17±0．05,130．84±5．72 vs 158.37±6．64,P<0．05),治疗组对于酒精组有所下降(0.30±0．04 vs 0．41±0．13,149．23± 6．65 vs 130．84±5．72．P<0．05)．结论:小剂量全反式维甲酸通过降低慢性酒精性肝损伤大鼠肝脏致纤维化因子TGF-β1, CTGF和Collal的表达抑制早期酒精性肝纤维化的形成．AIM： To investigate the role of all-trans retinoic acid （ATRA） in the early stage of alcoholic liver fibrosis in rats, by observing its effect on the expression of transforming growth factor β1 （TGF-β1）, connective tissue growth factor （CTGF） and pro alpha 1 （ Ⅰ ） collagen （Col1a1）. METHODS： Twenty-four rats were randomly and averagely divided into three groups, named J, A, and N. The rats in group J was given the mixture of ethanol and corn oil, and those in group A were added ATRA [0.15 mg/（kg·d）] after treatment with the same mixture for 8 wk. The animals in group N served as the controls, treating with the same amount of normal saline plus corn oil. All the mixtures were given intragastrically. All the animals were killed after 16 weeks. The histological changes of liver tissues were observed under light and electron microscope. The concentration of hepatic retinoic acid was examined using high-performance liquid chromatography （HPLC）. The expression of TGF-β1, CTGF and Col1a1 mRNA were measured by reverse transcription-polymerase chain reaction （RT-PCR）. The protein expression of TGF-β1 and CTGF were detected by immunohistochemistry. RESULTS： Ethanol intake led to alcoholic hepatitis. The swelling mitochondria and expanding endoplasmic reticulum were observed under electron microscope in the rats of group J. The damage was partially alleviated in group A. The concentration of hepatic retinoic acid was significantly decreased in group J than that in group N and A （76.7 ± 29.1 pmol/g vs 182.6 ± 37.2, 182.8 ± 273.8 pmol/g, P 〈 0.05）, while it was not markedly different between group A and N. The expression of Col1a1 mRNA was 0.10 ± 0.02, 0.18 ± 0.03, and 0.14 ± 0.03 in group N, J and A, respectively, and significant difference existed between either two groups （P 〈 0.05 or P 〈 0.01）. Ethanol treatment elevated the protein and mRNA expression of TGF-β1 （gray level： 105.9 ± 10.1 vs 149.3 ± 10.2, P 〈 0.01; mRNA： 0.53 ± 0.17 vs 0.34 ± 0.0

关 键 词：酒精性肝病 全反式维甲酸 转化生长因子 β1 结缔组织生长因子 Ⅰ型胶原前胶原α1基因 

分 类 号：R575[医药卫生—消化系统]