间断注射骨钙素可预防高脂饮食诱导小鼠非酒精性脂肪性肝病的发生  

Intermittent injection of osteocalcin prevents high fat diet-induced nonalcoholic fatty liver disease in mice

作　　者：聂美云[1] 张明亮[1] 杜婧[1] 窦建新[1] 陆俊茜[1] 马晓静[1] 包玉倩[1] 贾伟平[1] 

机构地区：[1]上海交通大学附属第六人民医院内分泌代谢科,上海市糖尿病临床医学中心,上海市代谢病临床医学中心,上海市糖尿病研究所,上海市糖尿病重点实验室,上海200233

出　　处：《中华老年多器官疾病杂志》2014年第11期857-862,共6页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家自然科学基金（81170788）;上海市科学技术委员会科研计划项目（13XD1403000）

摘　　要：目的：探讨外源性骨钙素干预是否可预防高脂饮食诱导的野生型小鼠非酒精性脂肪性肝病（NAFLD）的发生。方法将5周龄C57BL/6J雄性小鼠随机分为4组：（1）普通饮食对照组；（2）高脂饮食对照组；（3）高脂饮食＋骨钙素低剂量组；（4）高脂饮食＋骨钙素高剂量组。实验期间监测体质量、血糖、进食量等指标；实验结束后，检测血清总胆固醇（TC）、甘油三酯（TG）、游离脂肪酸（FFA）、肿瘤坏死因子α（TNF-α）等指标，并行肝组织学检查及肝TC、TG含量测定。HE染色和油红O染色观察肝形态学改变。结果（1）与高脂饮食对照组相比，两种不同剂量骨钙素干预组的体内脂肪含量，包括附睾旁脂肪、肾周脂肪、皮下脂肪及脂体比均明显降低（均P＜0.001）；空腹血糖及葡萄糖耐量较高脂对照组明显改善（P＜0.05～0.001）；血清TC、TG、FFA、TNF-α等指标较高脂对照组明显降低（均P＜0.05）；（2）两种不同剂量骨钙素干预组的肝脂肪沉积明显减少，肝质量、肝体比、肝TC及TG含量等指标均较高脂饮食对照组明显降低（均P＜0.05）。结论骨钙素间断注射可有效预防高脂饮食诱导小鼠NAFLD的发生，改善糖脂代谢，并可降低血清TNF-α水平。Objective To investigate whether exogenous osteocalcin intervention prevents high fat diet-induced nonalcoholic fatty liver disease （NAFLD） in wild type mice. Methods Five-week-old C57Bl/6J male mice were randomly divided into 4 groups, that is, normal diet, high fat diet, and high fat diet＋osteocalcin 3 or 10ng/（g＆#183;d） groups. The body mass, blood glucose, and food intake were monitored during the 24 weeks’ experiment. Serum levels of total cholesterol （TC）, triglycerides （TG）, free fatty acid （FFA）, and tumor necrosis factorα（TNF-α） and liver contents of TC and TG were measured at the end of the study. Oil Red O and hematoxylin-eosin staining were performed to observe the morphology of the livers. Results Compared with high fat diet group, the groups treated by different doses of osteocalcin had significantly decreased total fat mass （including the fat around epididymides and kidneys as well as subcutaneous fat） and total fat mass/body mass ratio （P〈0.001）, better fasting blood glucose and glucose tolerance （P〈0.05？0.001）, and obviously reduced serum levels of TC, TG, FFA and TNF-α （P〈0.05）. Osteocalcin treatment prevented high fat diet-induced liver steatosis and resulted in remarkably decreased liver mass, ratio of liver mass to body mass as well as liver TC and TG levels （P〈0.05）. Conclusion Intermittent injection of osteocalcin significantly prevents high fat diet-induced NAFLD, improves glucose-lipids metabolism and reduces serum TNF-αlevel.

关 键 词：脂肪肝 骨钙素 肝脂质 

分 类 号：R575.5[医药卫生—消化系统]