高脂饮食法构建小鼠非酒精性脂肪性肝病模型雌雄TLR4及IL-6表达的差异  

The gender different expression of TLR4 and IL-6 in NAFLD mice induced by high fat diets

作　　者：赵雪[1] 梁志清[1] 白纪红[1] 林秋香[1] 张茂华[1] 彭名人 

机构地区：[1]桂林医学院附属医院感染性疾病科,广西桂林541004

出　　处：《广东医学》2013年第24期3712-3716,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81260078);广西自然科学基金资助项目(编号:2012GXNSFAA276038);广西壮族自治区卫生厅自筹经费科研课题(编号:Z2012421);广西桂林市科学研究与技术开发计划项目(编号:20090539)

摘　　要：目的观察高脂饮食法构造小鼠非酒精性脂肪性肝病(NAFLD)模型Toll样受体4(TLR4)及白细胞介素-6(IL-6)的雌雄差异。方法 120只昆明小鼠,雌雄各半分别随机分为对照组和模型组,雌雄分笼饲养。对照组及模型组分别予普通饲料及高脂饲料喂养,于喂养第8、12、16周后分别于各组随机处死10只,观察各组肝脏外观及其病理变化,计算肝指数、体重差,采用流式细胞术及RT-PCR法检测TLR4的表达,ELISA法检测IL-6,全自动生化分析仪检测三酰甘油(TG)、血清总胆固醇(TC)和丙氨酸转移酶(ALT)。结果雌性模型组小鼠无或仅有少数细胞发生脂肪变性,雄性模型组小鼠均有严重程度不等的脂肪变性,第8、12周间比较差异无统计学意义,第16周组明显高于第8、12周(P<0.01),同周次处死的小鼠模型组雄性脂肪变程度明显高于雌性(P<0.05)。体重差、肝重、TG、TC、ALT、IL-6、TLR4结果分析显示,模型组除第8周雌雄间IL-6差异无统计学意义外,雌雄间比较均有统计学意义(P<0.05),雄性高于雌性;同性别的小鼠比较,除RT-PCR法检测TLR4基因表达的结果第8周雌性小鼠与对照组比较无差异外,模型组各指标均高于其相应的对照组(P<0.05)。对照组不同时间各组比较,差异无统计学意义,模型组不同时间各组比较差异均有统计学意义(P<0.05),随时间延长而升高。结论高脂饮食法对昆明小鼠进行NAFLD造模会上调其TLR4和IL-6的表达,雄性小鼠比雌性小鼠更为显著,因此,通过高脂饮食法构建NAFLD模型,尤其是研究NAFLD宜选用雄性小鼠。Objective To investigate the gender different expression of TLR4 and IL - 6 in NAFLD Kunming mice induced by high fat diets. Methods A total of 120 Knnming mice （male 60） were randomly divided into normal control group and model group, in which normal diet and high fat diet were given, respectively. Each 10 male and 10 female mice from both groups were randomly selected for sacrificed at 8^th, 12^th and 16th week. The appearance and pathological changes of liver was observed, while the liver index and weight difference were calculated. The expression of TLR4, IL- 6, TG, Tch and ALT were determined. Results Significantly severer fatty changes in liver was observed in male model mice than female ones at 16^th week （ P 〈 0. 05 ） , which was also significantly more prominent than those at 8^th or 12^th week （P 〈0. 01 ）. Significant elevation in body weight, liver weight, TG, Tch, ALT, IL-6 and TLR4 was observed in the male model mice （P 〈 0. 05 ） , except for in IL- 6 at 8^th week. Significantly elevation in all indexes in both male and female model mice than those of controls （ P 〈 0. 05 ） , except for in TLR4 expression in female mice at 8^th week. And the longer the model group were fed with high fat diet, the significantly higher the indexes were observed （ P 〈 0. 05 ）. Conclusion TLR4 and IL- 6 in NAFLD mice induced by high fat diets are up -regulated, especially in male mice, which providing better NAFLD model.

关 键 词：非酒精性脂肪性肝病 TOLL样受体-4 白细胞介素-6 流式细胞术 雌雄差异 

分 类 号：R575.5[医药卫生—消化系统]