选择性雌激素受体调节剂对小鼠肥胖及脂代谢的作用  

Effects of selective estrogen receptor modulator tamoxifen on obesity and lipid metabolism in mice

作　　者：朱晶[1] 傅晓华[1] 张岭[1] 金碧辉[1] 舒静[1] ZHU Jing;FU Xiaohua;ZHANG Ling(Department of Reproductive Endocrinology,Zhejiang Provincial People＇s Hospital（People＇s Hospital of Hangzhou Medical College）,Hangzhou 310014,China)

机构地区：[1]浙江省人民医院/杭州医学院附属人民医院生殖内分泌科,杭州310014

出　　处：《浙江医学》2018年第12期1295-1298,共4页Zhejiang Medical Journal

基　　金：浙江省自然科学基金青年基金项目(LQ18H040004);浙江省医药卫生科技计划项目(2016KYA029)

摘　　要：目的探讨选择性雌激素受体调节剂(SERMs)对小鼠肥胖和脂代谢的作用。方法采用随机数字表法将32只8周龄C57/BL6雌鼠分为假手术组、卵巢切除组、假手术他莫昔芬组、卵巢切除雌激素替代组4组,每组8只。假手术组小鼠腹腔注入0.3%戊巴比妥钠麻醉(0.25ml/10g),打开腹腔暴露卵巢不作处理,随即关闭腹腔;卵巢切除组小鼠腹腔注入0.3%戊巴比妥钠麻醉后行双侧卵巢切除术;假手术他莫昔芬组小鼠麻醉后行假手术,术后每周1次皮下注射他莫昔芬缓释剂0.1ml;卵巢切除雌激素替代组小鼠行双侧卵巢切除术后,皮下埋植17β-雌二醇(E_2)缓释剂。予以高脂饲料喂养8周后,比较各组小鼠体重增加量、皮下脂肪/体重比值及内脏脂肪/体重比值、糖耐量、胰岛素抵抗指数(HOMA-IR)、血清E_2水平、脂代谢指标TG、TC、HDL-C、LDL-C和血清脂联素(ADPN)水平。结果高脂饲料喂养8周后,假手术他莫昔芬组小鼠体重增加量最少,E_2水平明显下降,血清TC、HDL-C水平也最低,差异均有统计学意义(均P<0.05);此外,该组小鼠皮下脂肪/体重比值及内脏脂肪/体重比值也显著低于卵巢切除组(均P<0.05),糖耐量水平明显改善(P<0.05),血清ADPN水平也明显高于卵巢切除组(P<0.05),但与卵巢切除雌激素替代组比较差异无统计学意义(P>0.05)。结论 SERMs显著降低血清雌激素水平,对小鼠脂肪蓄积、再分布及血清脂代谢指标有一定的改善作用。Objective To investigate the effect of selective estrogen receptor modulator tamoxifen on obesity and lipid metabolism in mice. Methods Thirty two female C57/BL6 mice of 8 weeks were randomly divided into 4 groups： sham group,OVX group, Sham＋TAM and OVX ＋E2 with 8 mice in each group. Sham group：0.3% pentobarbital sodium（0.25 ml/10 g） was injected into the abdominal cavity, the ovary was exposed before the abdominal cavity was closed. OVX group： bilateral ovariectomy was performed after the mice were anesthetized. Sham＋TAM group： sham operation was performed and 0.1 ml sustained-release tamoxifen was injected subcutaneously once a week after surgery. OVX ＋E2 group： bilateral ovariectomy was performed,sustained-release E2 was implanted subcutaneously. After giving high-fat diet for 8 weeks, body weight, subcutaneous and visceral fat weight, glucose tolerance, insulin resistance（HOMA-IR） and serum lipid metabolism related factors were compared among 4 groups. Results The serum estrogen level of Sham＋TAM group was decreased, however, its weight gain was the lowest and the serum TC level was also the lowest（all P〈0.05）; in addition, the visceral fat weight of Sham＋TAM group was lower than that of OVX group（P〈0.05）, the glucose tolerance was improved（P〈0.05）, serum adiponectin（ADPN） level was higher than OVX group（P〈0.05）, but there was no significant difference when comparing with OVX＋E2 group（P〈0.05）. Conclusion The elective estrogen receptor modulator tamoxifen can significantly reduce the serum estrogen level, at the same time, it also has a positive effect on the body fat accumulation, redistribution and lipid metabolism.

关 键 词：雌激素 选择性雌激素受体调节剂 肥胖 脂代谢 

分 类 号：R589.2[医药卫生—内分泌]