瘦素及其肝脏受体在大鼠NAFLD形成过程中的变化及意义

Leptin and expression of leptin receptor in hepatocyte in nonalcoholic fatty liver rats

目的探讨瘦素及瘦素受体在非酒精性脂肪肝病(NAFLD)发病机制中的可能作用。方法Wistern雄性大鼠36只,体重在(200±20)g/只,随机分为高脂饮食组(F组)与正常对照组(C组)。以高脂饮食喂养12周,建立NAFLD大鼠模型,基础饮食为对照组。高脂饮食组设4、8、12周3个时相点。动态观察大鼠体重变化,放射免疫法检测大鼠血清瘦素浓度,光镜下观察肝脏脂肪变情况,并进行脂肪变分度及炎症分级,免疫组织化学法观察瘦素受体在正常大鼠肝脏及非酒精性脂肪肝形成过程中的表达变化,Western-Blot检测表达量。结果F组肝脏体积显著>C组(P<0.05);F组的大鼠血清瘦素浓度显著高于正常对照组(P<0.05),且随着脂肪变程度的加重,血清瘦素浓度有升高趋势;瘦素受体的表达在高脂饮食早期即有增加,且在肝脏的表达随着肝脏脂肪变的加重有增加趋势,尤其在重度脂肪肝肝细胞中表达明显。结论血清瘦素浓度在大鼠NAFLD的形成中逐渐升高,瘦素受体在NAFLD形成过程中在肝脏表达上调,瘦素及其受体可能参与了NAFLD肝脏能量代谢紊乱的发生。

Objective To investigate the effect of leptin and leptin receptor on hepatocyte in nonalcoholic fatty liver rats. Methods A total of 36 Wistar rats were randomly divided into the basic diet-control group （Group C） and the high-fat diet group （Group F）. Each of the two groups was subdivided into 3 subgroups （4, 8,12 weeks） （6 cases in each group）. Changes in animal weight were observed dynamically,expressions of leptin receptor detected by Western blotting and immunohistochemistry in each subgroup. Leptin level in serum was detected by radioimmunoassay. Results Animal weight in Group F was significantly higher than that in Group C （P〈0.01）. Serum leptin level of Group F was higher than that in Group C （P〈0.05）. Protein expressions of leptin receptor particularly at 4,8,12 week increased in a time-dependent manner with significant difference as compared with those in Group C at 12 week（P〈0.05）. Conclusion The increase of leptin in serum and leptin recptor in liver may be concerned with energy disorder in NAFL rats.