【摘要】 目的:探讨脂肪组织中TNF-α基因表达与神经肽Y(NPY)Y5受体反义基因减肥降脂作用的关系。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,观察肥胖大鼠腹腔内脂肪组织湿重与血脂的变化,采用RT-PCR技术检测腹膜后脂肪组织中TNF-α基因的表达水平。结果:①高营养饮食诱导下,肥胖大鼠腹腔内脂肪组织湿重与血脂水平均明显高于正常大鼠,腹膜后脂肪组织中TNF-α基因的表达:水平则显著高于正常大鼠;②NPYY5受体反义寡核苷酸干预后,肥胖大鼠腹腔内脂肪组织湿重与血脂水平均明显降低,腹膜后脂肪组织中TNF-α基因的表达水平则显著低于肥胖对照大鼠。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TNF-α基因的表达下调有关。更多还原

【Abstract】 Objective: To study the role of TNF-α gene in neuropeptide Y Y5 receptor antisense gene therapy of diet-induced obese rats. Methods: The diet-induced obese rats were prepared by feeding a high-nutritive diet for 7 weeks. After the lateral ventricular an-nulization was performed in obese rats, the different neuropeptide Y Y5 receptor oligodeoxynucleotides (including antisense oligodeoxynucleotide and mismatched oligodeoxynucleotide) or saline were administered intracerebroventricularly three dmes per day for 2 days. When the rats were slaughtered, the wet weight of abdominal adipose tissue, the level of serum lipids were measured. Total RNA from the retroperitoneal adipose tissue was extracted and the level of TNF-a gene mRNA expression was analyzed by RT-PCR. Results: ① The wet weight of abdominal adipose tissue, the levels of serum lipids, and the level of TNF-α gene mRNA expression in adipose tissue were significantly higher in diet-induced obese rats than those in normal rats. ② After NPY Y5 receptor antisense oligodeoxynucleotide were intracerebroventricularly administrated in diet-induced obese rats, the level of TNF-α gene mRNA expression in adipose tissue of diet-induced obese rats was significantly down-regulated, while the wet weight of abdominal adipose tissue and the levels of serum lipids were significantly reduced. Conclusion: Intracerebroventricular administration of neuropeptide Y Y5 receptor antisense oligodeoxynucleotide could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats. The mechanism may be related to the down-regulated expression of TNF-α gene mRNA in retroperitoneal adipose tissue.更多还原