胃饥饿素拮抗剂（D-赖氨酸3）GHRP-6对成年雌性白化大鼠卵巢切除诱导肥胖的影响。

The effect of ghrelin antagonist (D-Lys3) GHRP-6 on ovariectomy-induced obesity in adult female albino rats.

作者信息

Abdel-Hakim S M, Ibrahim M Y, Ibrahim H M, Ibrahim M M

出版信息

Endocr Regul. 2014 Jul;48(3):126-34. doi: 10.4149/endo_2014_03_126.

DOI:10.4149/endo_2014_03_126

PMID:25110211

Abstract

OBJECTIVE

We aimed to investigate the effect of ghrelin antagonist (D-Lys3) GHRP-6 on the treatment of ovariectomy-induced obesity as compared to hormone replacement therapy with estradiol.

METHODS

Twenty eight rats were divided into four groups: control sham operated (C), ovariectomized non-treated (OVX), ovariectomized+estradiol-treated (OVX+E) groups, and ovariectomized+ghrelin antagonist-treated group (OVX+GA). Rats were allowed free water and commercial standard diet ad libitum for 5 weeks after surgery. Body mass index (BMI) was determined at the beginning and the end of the experiment. Rats were sacrificed by decapitation and blood samples were collected for measurements of serum lipid profile, insulin, and glucose levels. Gastrocolic omental fat (GCOF) was removed and weighed.

RESULTS

Ovariectomy was accompanied with a significantly higher body weight, food intake, BMI, GCOF, serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), glucose, insulin, and homeostatic model assessment - insulin resistance (HOMA-IR), with a significant decrease in high density lipoprotein-cholesterol (HDL-C) and triglycerides (TGs) in comparison with C group. Estradiol reversed the ovariectomy-induced changes except that of TGs. Administration of ghrelin antagonist was effective in treating the ovariectomy-induced obesity as evidenced by normalization of body weight, food intake, BMI, and GCOF weight, serum levels of insulin, glucose, HOMA-IR, and HDL-C. The serum levels of TC, LDL-C and TGs were improved but did not reach the control values.

CONCLUSION

Although estradiol succeeded in the prevention of almost all ovariectomy-induced disturbances, it had a potential cardiovascular risk due to a marked increase in serum TGs. Ghrelin antagonist was effective in ameliorating ovariectomy-induced obesity, so it may be used as a promising treatment for postmenopausal obesity, irrespective of hormonal replacement.

摘要

目的

我们旨在研究与雌二醇激素替代疗法相比，胃饥饿素拮抗剂（D - Lys3）GHRP - 6对去卵巢诱导的肥胖症的治疗效果。

方法

将28只大鼠分为四组：假手术对照组（C）、去卵巢未治疗组（OVX）、去卵巢+雌二醇治疗组（OVX + E）和去卵巢+胃饥饿素拮抗剂治疗组（OVX + GA）。术后5周，让大鼠自由饮水并随意进食商业标准饮食。在实验开始和结束时测定体重指数（BMI）。通过断头处死大鼠，采集血样以测量血清脂质谱、胰岛素和葡萄糖水平。去除并称重胃结肠网膜脂肪（GCOF）。

结果

与C组相比，去卵巢伴随着体重、食物摄入量、BMI、GCOF、血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL - C）、葡萄糖、胰岛素和稳态模型评估 - 胰岛素抵抗（HOMA - IR）显著升高，高密度脂蛋白胆固醇（HDL - C）和甘油三酯（TGs）显著降低。除TGs外，雌二醇逆转了去卵巢诱导的变化。胃饥饿素拮抗剂的给药有效治疗了去卵巢诱导的肥胖症，体重、食物摄入量、BMI和GCOF重量、胰岛素、葡萄糖、HOMA - IR和HDL - C的血清水平恢复正常证明了这一点。血清TC、LDL - C和TGs水平有所改善，但未达到对照值。