大鼠非酒精性脂肪性肝炎模型的铁状态

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摘要［摘要］目的: 动态观察甲硫氨酸胆碱缺乏（methioninecholinedeficient, MCD）模型饲料诱导的非酒精性脂肪性肝炎（nonalcoholic steatohepatitis, NASH）雄性大鼠在不同时间点铁状态以及铁状态改变与NASH进展的关系。方法: 48只体质量约150 g的SD大鼠随机分成两组，分别喂MCD模型饲料（模型组）和甲硫氨酸胆碱充足模型饲料（对照组），每组再按饲养时间分为3个小组（0周组、2周组、4周组）。在不同喂养时间结束时，处死大鼠。通过HE染色观察肝脏标本脂肪变性、炎症变化。血液标本测定红细胞相关指标、血清标本测定肝酶和铁相关指标；取肝脏匀浆测定非血红素铁（nonheme iron,NHI）含量。结果：喂养2周时，模型组肝指数较对照组显著升高，肝脏病理学切片可见明显脂肪变性伴有炎性细胞浸润，血清ALT显著增加，血红蛋白浓度、红细胞比容（Hct）显著降低，平均红细胞体积（MCV）、平均红细胞血红蛋白量（MCH）、红细胞分布宽度（RDW）无显著差异，血清铁、转铁蛋白饱和度（TS）和NHI明显高于对照组；4周时，模型组肝组织炎症程度加深，伴有血清AST显著增加，血红蛋白浓度、Hct和RDW显著降低，TS无显著差异，血清铁显著高于对照组。结论： MCD模型饲料诱导的肝脏NASH进程中，发生肝铁过载，铁过载与NASH形成和发展初期同步，铁过载伴有血液血红蛋白浓度、Hct和RDW降低，这些降低不是铁缺乏性，其机制可能涉及骨髓造血功能抑制。

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关键词 ：甲硫氨酸胆碱缺乏, 非酒精性脂肪性肝炎, 铁状态, 非血红素铁, 大鼠

Abstract：［Abstract］Objective： To establish a rat model of nonalcoholic steatohepatitis (NASH) by feeding a methioninecholinedeficient (MCD) diet and monitor the iron status dynamically at different periods. Methods：A total of 48 male SpragueDawley rats were randomly divided into 2 groups: one treated with MCD diet (model group) and the other treated with methioninecholinesufficient diet (control group),and then each were divided into three subgroups according to three feeding periods (0, 2 and 4 weeks). At the end of their different periods, the rats were sacrificed. Liver index, morphology of liver tissue was detected by HE staining. Serum ALT and AST, blood Hb concentration, Hct, MCV, MCH and RDW, serum iron(SI) and transferrin saturation(TS), and hepatic nonheme iron(NHI) contents were also determined. Results：The model group in the 2weeks group had a significant increase of liver index, and obvious steatosis with inflammatory cells infiltration and a significant increase of ALT. In this group, Hb concentration and Hct were significantly decreased without change in MCV, MCH and RDW, and SI concentration and TS and hepatic NHI contents were significantly increased. In the 4weeks group, the model group had become deterioration in morphology of liver tissue with a significant increase in AST and a significant decrease in RDW with similar level of TS to their control group, while the Hb, Hct and SI maintained significantly different from their control groups. Conclusion：In the MCD dietinduced NASH model, iron overload might be involved in the formation and development of NASH; the iron overload is accompanied by decreases in blood Hb concentration,Hct and RDW which are not irondeficient, but possibly associated with suppressive hematopoiesis of bone marrow.

基金资助:

［基金项目］国家自然科学基金资助项目( 31071038)

通讯作者: 肖德生（通讯作者），教授，博士生导师，E-mail：dsxiao@gzmu.edu.cn

作者简介: ［作者简介］陆美婷（1990—），女，硕士研究生

引用本文:

陆美婷，张立威，习文韬，曾淳子，肖德生. 大鼠非酒精性脂肪性肝炎模型的铁状态[J]. 江苏大学学报:医学版, 2016, 26(04): 277-282. LU Mei-ting， ZHANG Li-wei， XI Wen-tao， ZENG Chun-zi， XIAO De-sheng. Evaluation of iron status in a nonalcoholic steatohepatitis rat model. Journal of Jiangsu University(Medicine Edition), 2016, 26(04): 277-282.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2016/V26/I04/277

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