1,25-二羟基维生素D_3对大鼠非酒精性脂肪性肝炎的防治作用及机制  

Preventive and therapeutic effect of 1,25-dihydroxyvitamin D_3 on non-alcoholic steatohepatitis of rats

作　　者：韩红梅[1] 陈梅花[1] 朴东明[2] 崔明花[3] 朴熙绪[1] 

机构地区：[1]延边大学附属医院消化内科,吉林延吉133000 [2]延边大学附属医院病理科,吉林延吉133000 [3]延边大学医学院病理学教研室,吉林延吉133000

出　　处：《中国药理学与毒理学杂志》2015年第1期48-54,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：延边大学科技发展项目~~

摘　　要：目的探讨1,25-二羟基维生素D3〔1,25(OH)2D3〕对非酒精性脂肪性肝炎(NASH)的防治作用及可能的机制。方法将雄性Wistar大鼠采用(自由摄取)胆碱缺乏氨基酸(CDAA)饮食诱导建立NASH模型的同时,每周2次(周二和周六)ip给予1,25(OH)2D31,5和10μg·kg-1。第12周末,测量大鼠体质量、肝质量,计算肝指数;检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、甘油三酯(TG)、总胆固醇(CHO)和肝组织TG水平;苏木素和伊红染色、天狼星红染色观察肝组织形态学变化;免疫组织化学法检测CD68、转化生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达。结果与正常组相比,模型组大鼠肝指数明显增加(P<0.01);血清GPT和GOT和肝组织TG水平明显升高(P<0.01),血清CHO水平升高(P<0.05),肝组织NAS积分和CD68,TGF-β1和α-SMA的表达明显升高(P<0.01)。与模型组相比,给予1,25(OH)2D3治疗后,5μg·kg-1剂量组肝指数下降(P<0.05);血清GPT和GOT活性均明显下降(P<0.05);5μg·kg-1剂量组血清TG水平显著升高(P<0.01);5μg·kg-1剂量组肝组织TG水平、NAS积分和CD68,TGF-β1,α-SMA表达明显降低(P<0.05)。结论 1,25(OH)2D3可通过抑制肝组织的CD68、TGF-β1和α-SMA蛋白表达改善NASH大鼠炎症。OBJECTIVE To investigate the preventive and therapeutic effect of 1,25-dihydroxyvitamin D3〔1,25（ OH）2D3〕on non-alcoholic steatohepatitis（ NASH） in rats and its potential mechanism.METHODS Male Wistar rats were subjected to free uptake of a choline deficient amino acid-defined（ CDAA） diet,and were used as a diet-induced NASH model by ip of 1,5 or 10 μg·kg- 11,25（ OH）2D3,respectively,twice a week（ Tuesday and Saturday）,for 12 weeks. The body mass,liver mass and liver index in rats,and serum levels of glutamic-pyruvic transaminase（ GPT）,glutamic-oxalacetic transaminase（ GOT）,triglycerides（ TG）,total cholesterol（ CHO） and hepatic level of TG were determined.Hepatic histology was examined by hematoxylin / eosin（ HE） and Sirius red staining,and expression levels of CD68,transforming growth factor beta1（ TGF-β1） and α-smooth muscle actin（ α-SMA） were analyzed by immunohistochemical method in the liver. RESULTS Compared to the normal group,the liver index,serum levels of GPT and GOT and hepatic levels of TG in CDAA-diet induced NASH rats were significantly increased（ P 0. 01）,serum levels of CHO were increased（ P 0. 05）,NAS scores and expression levels of CD68,TGF-β1and α-SMA were significantly increased in the liver（ P 0. 01）.Compared to the NASH rats,1,25（ OH）2D3treatment showed that the liver index（ 5 μg·kg- 1,P 0.05） and serum levels of GPT and GOT（ P 0. 05） were reduced,but serum levels of TG were significantly increased（ P 0. 01）. Moreover,hepatic levels of TG,NAS scores and expression levels of CD68,TGF-β1and α-SMA were reduced（ 5 μg·kg- 1,P 0. 05）. CONCLUSION 1,25（ OH）2D3can protect against NASH by inhibiting expressions of CD68,TGF-β1and α-SMA in the liver.

关 键 词：1 25-二羟基维生素D3 非酒精性脂肪性肝炎 CD68 转化生长因子Β1 Α-平滑肌肌动蛋白 

分 类 号：R575.1[医药卫生—消化系统]