雌激素对CETP转基因小鼠糖代谢及胰岛功能影响的初步研究

The effect of estrogen on glucose metabolism and islet function in CETP transgenic mice

目的:观察CETP转基因小鼠在卵巢切除和雌激素替代情况下糖耐量和胰岛功能的改变。方法:15只雌性CETP转基因小鼠随机分为3组,假手术组、卵巢切除组和雌激素替代组。除假手术组外,其余均行卵巢切除术。术后第2周开始,雌激素替代组给予雌激素治疗,而假手术组和卵巢切除组则给予同等剂量的橄榄油,4周后检测各组小鼠空腹血糖,8周后进行腹腔注射葡萄糖耐量(IPGTT)试验,提取小鼠胰岛做葡萄糖刺激的胰岛素分泌(GSIS)实验。结果:术后8周,卵巢切除组小鼠空腹血糖较假手术组鼠明显升高(P<0.05),IPGTT各时点血糖均较假手术组小鼠明显升高(P<0.05),GSIS显示胰岛素分泌功能有减退的趋势;而雌激素替代组上述变化有明显改善,IPGTT的0、15、30 min的血糖水平显著下降(P<0.05),GSIS的胰岛素分泌功能也有改善的趋势。结论:CETP转基因小鼠卵巢切除后胰岛功能下降,表现为空腹血糖升高、糖耐量受损、葡萄糖刺激的胰岛素分泌水平下降。雌激素替代能够对卵巢切除所带来的对于胰岛β细胞的有害影响起到一定的保护作用。

Objective：To observe changes of glucose tolerance and insulin function of CETP transgenic mice with ovariectomy and estrogen replacement.Methods：Fifteen female CETP transgenic mice were randomly divided into three groups,including the sham group,the ovariectomy group and the estrogen replacement therapy group.The ovariectomy group and the estrogen replacement therapy group were underwent ovariectomy.Two weeks after operation,the estrogen replacement therapy group was given estrogen,while the sham group and the ovariectomy group were given equal dosages of olive oil.Fasting glucose was measured four weeks after operation.Islets were extracted to test islet function by intraperitoneal glucose tolerance test（IPGTT）and GSIS eight weeks after operation.Results：Mice of the ovariectomy group showed significantly increased fasting glucose levels 8 weeks after operation compared with those of the sham group（P〈0.05）.The blood glucose of mice at all time points of IPGTT increased significantly than those in the sham group（P〈0.05）.GSIS showed that insulin secretion had a decreased tendency.While after ovariectomy,estrogen replacement therapy significantly improved the above changes.Blood glucose levels at 0,15 and 30 min of IPGTT were decreased significantly（P〈0.05）.Insulin secretion function of GSIS also had an improved tendency.Conclusion：After ovariectomy,CETP transgenic mice have impaired islet function and glucose tolerance,which lead to the increase of fasting blood glucose and the decrease of glucose stimulated insulin secretion levels.Estrogen replacement plays a protective role in the harmful effects of ovariectomy on pancreatic is let βcells.