β3肾上腺素能受体基因在肥胖大鼠神经肽Y Y5受体反义基因治疗中的作用

摘要

Objective: To study the role of β3-adrenergic receptor gene in neuropeptide Y(NPY) Y5 receptor antisense gene therapy of diet-induced obese rats. Methods: The diet-induced obese rats were prepared by feeding a high-nutrition diet. Lateral ventricular was cannulated in obese rats which then received an intraventricular injection of either 5 μg/μl NPY Y5 receptor antisense or 10 μl missense oligodeoxynucleotide or saline of 10 μl respectively in every rat. When the rats were killed, the wet weight of abdominal adipose tissue, the level of serum lipid and lipoprotein were measured. Total RNA from the retroperitoneal adipose wet weight of abdominal adipose tissue, the levels of serum lipids were greatly higher in diet-induced obese rats than those in normai rats. However, there were much lower β3-adrenergic receptor gene mRNA expression levels in retroperitoneal adipose tissue istered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue of diet-induced obese rats were strikingly up-regulated, whereas the wet weight of abdominal adipose tissue, the levels of serum lipids were markedly reduced. Conclusion: Intraventricular administration of antisense oligodeoxynucleotide to NPY Y5 receptor could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats by up-regulating the level of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.%目的:探讨β3肾上腺素能受体基因在肥胖大鼠神经肽Y(NPY)Y5受体反义基因治疗中的作用.方法:建立高营养饮食诱导的肥胖大鼠模型,侧脑室插管后注射NPY Y5受体反义、错义寡核苷酸或生理盐水,测定肥胖大鼠的腹腔内脂肪组织湿重与血脂,并采用RT-PCR技术检测腹膜后脂肪组织中β3肾上腺素能受体基因的表达水平.结果:①高营养饮食诱导下肥胖模型大鼠的腹腔脂肪组织湿重与血脂水平均明显高于正常大鼠;②经NPY Y5受体反义寡核苷酸干预后,肥胖大鼠的腹腔脂肪组织湿重与血脂水平均明显降低,腹膜后脂肪组织中β3肾上腺素能受体基因的表达水平则显著高于肥胖对照大鼠.结论:侧脑室注射NPY Y5受体反义寡核苷酸可显著降低肥胖大鼠的体脂、血脂,其机制可能与腹膜后脂肪组织β3肾上腺素能受体基因的表达上调有关.