实用肝脏病杂志 ›› 2021, Vol. 24 ›› Issue (5): 657-660.doi: 10.3969/j.issn.1672-5069.2021.05.013

• 实验性肝炎 • 上一篇    下一篇

门冬氨酸鸟氨酸对非酒精性脂肪性肝炎合并肌少症性肥胖小鼠的保护作用*

王子璇, 王梦雨, 李经纬, 杨蕊旭, 曾静, 潘勤, 范建高   

  1. 200092 上海市 上海交通大学医学院附属新华医院消化内科
  • 收稿日期:2021-01-12 发布日期:2021-10-21
  • 通讯作者: 范建高,E-mail: fattyliver2004@126.com
  • 作者简介:王子璇,女,25岁,医学硕士。E-mail: zixuanwang2020@126.com
  • 基金资助:
    *国家科技部精准诊疗课题(编号:2017YFSF090203);国家自然科学基金面上项目(编号:81873565/81900507);上海市领军人才培养计划项目(编号:2017019);上海交通大学医学院附属新华医院临床研究培育基金资助项目(编号:2017CSK04)

Protective effects of L-ornithine L-aspartate on mice with nonalcoholic steatohepatitis and sarcopenic obesity

Wang Zixuan, Wang Mengyu, Li Jingwei, et al   

  1. Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China
  • Received:2021-01-12 Published:2021-10-21

摘要: 目的 探讨应用门冬氨酸鸟氨酸对非酒精性脂肪性肝炎(NASH)和肌少症性肥胖小鼠的干预作用。方法 将28只雄性C57B/b小鼠随机分为对照组11只和模型组17只,分别给予普通饮食和高脂饮食饲养,在12周末将两组小鼠各随机处死5只以验证NASH模型。将其余模型组小鼠随机分为模型对照组6只和干预组6只,给予等量生理盐水或门冬氨酸鸟氨酸溶液灌胃,共8周。在透明动物仓内插入Minispec LF50小动物MRI体成分分析仪检测小鼠全身脂肪和肌肉质量,使用BIO-GS3握力计测量小鼠前肢抓力。结果 在实验12周,成功建立NASH模型;模型组小鼠抓力显著低于对照组;在第20周,模型对照组体脂质量和体脂率分别为(8±0.7)g和(21.0±6.7)%,均显著高于对照组;干预组肝脂肪变、炎症和气球样变及骨骼肌病变程度均较模型对照组显著改善,体脂质量和体脂率分别为(3.7±0.3)g和(11.3±4.2)%,均较模型对照组显著降低(P<0.05);干预组瘦体质量和抓力均较模型对照组显著增加;干预组小鼠肌细胞形态饱满,肌纤维直径显著增加,肝组织非酒精性脂肪性肝病活动性积分显著下降,所有小鼠都达到了NASH缓解标准。结论 20周的高脂饮食可以成功制备小鼠NASH合并肌少症性肥胖模型,应用门冬氨酸鸟氨酸对肌少症性肥胖和NASH有一定程度的防治作用。

关键词: 非酒精性脂肪性肝炎, 肌少症性肥胖, 门冬氨酸鸟氨酸, 小鼠

Abstract: Objective The purpose of this study was to explore the intervening effect of L-ornithine L-aspartate (LOLA) on in mice with nonalcoholic steatohepatitis (NASH) and sarcopenic obesity. Methods 28 male C57BL/6 mice were randomly divided into control (n=11) and model group (n=17) and were fed with chow diet or high-fat diet, respectively. Five mice from each group were sacrificed to evaluate the establishment of NASH model after 12 weeks. The remaining mice fed with high fat diet were further randomized into the model control (n=6) and the intervention group (n=6) and were orally administrated with saline or LOLA solution once daily for 8 weeks. The pathological changes of liver and muscle were examined after execution. Results High-fat diet feeding for 12 weeks successfully established a NASH rodent model that presented with moderate-to-severe hepatic steatosis, lobular inflammatory cell infiltration, and hepatocyte ballooning; at the end of week 12, the grip strength of mice in model group was (100.2±1.8)g, significantly lower than in the control group; at the end of 20th week, the body fat mass and fat to body weight ratio of mice in the model control group were (8±0.7)g and (21.0±6.7)%, significantly higher than in the control group; the histopathological inflammatory severity of liver and muscle in the intervention group had significantly alleviated as compared to those in the model control group; the body fat mass and fat to body weight ratio in the intervention group were (3.7±0.3)g and (11.3±4.2)%, significantly lower than in the model control group (P<0.05); the lean body mass and grip strength in the intervention group were (75.2±2.7)% and (104.7±9.1)g, significantly higher than (64.7±3.2)% and (93.7±4.1)g in the model control group (P<0.05); in the intervention group, the muscle cells were normal with the diameter of muscle fibers increased, and the NAS score in liver tissues decreased, relieved NASH obtained in all mice. Conclusion s Twenty-week high-fat diet could establish a mouse model that simultaneously exhibits steatohepatitis and sarcopenic obesity, and the application of LOLA exerts some degree of protection to these two injuries.

Key words: Nonalcoholic steatohepatitis, Sarcopenic obesity, L-ornithine L-aspartate, Mice