摘要
目的 探讨神经肽Y(NPY)Y5受体基因反义寡核苷酸脑室给药对饮食所致肥胖大鼠外周瘦素抵抗的影响。方法 (1)建立高营养饲料诱导的肥胖大鼠模型 ,侧脑室插管后注射NPYY5受体基因反义、错义寡核苷酸及生理盐水 ,观察大鼠腹膜后脂肪湿重的变化 ;(2 )采用ELISA双抗体夹心法测定血清瘦素含量、放免法测定血清胰岛素含量 ,RT PCR技术检测脂肪组织中ob基因的表达水平 ,评价该疗法对肥胖大鼠外周瘦素抵抗的影响。结果 经NPYY5受体基因反义寡核苷酸干预后 ,肥胖大鼠腹膜后脂肪湿重、血清胰岛素含量、血清瘦素含量、腹膜后脂肪组织ob基因mRNA表达水平均明显降低 ,除腹膜后脂肪组织湿重与肥胖错义组差异未达到统计学意义外 ,其余指标与肥胖盐水组、肥胖错义组相比差异均有显著性 ,而肥胖错义组与肥胖盐水组之间各观察指标差异均无显著性。结论 侧脑室注射NPYY5受体基因反义寡核苷酸可显著减少营养性肥胖大鼠的腹膜后脂肪 ,降低肥胖大鼠脂肪组织ob基因表达及血清瘦素、胰岛素含量 。
Objective To study the effects of intracerebroventricular administration of antisense oligonucleotide to neuropeptide Y (NPY) Y5 receptor gene on the peripheral leptin resistance in diet induced obese rats. Methods Obese rats were induced by high nutrition feed for 7 weeks. Lateral ventricular catheterization was performed in obese rats for receiving an intracerebroventricular injection of either 10 μl/rat (5 μg/μl) neuropeptide Y Y5 receptor gene antisense or mismatched oligodeoxynucleotide or 10 μl saline three times per day for 2 days. After the rats were killed, the wet weight of retroperitoneal adipose tissue was measured and the serum insulin and leptin were detected by radioimmunoassay and ELISA, respectively. Total RNA from the retroperitoneal adipose tissue was extracted and the level of NPY Y5 gene mRNA expression was evaluated by RT PCR. Results The wet weight of retroperitoneal adipose tissue, the levels of serum insulin and leptin, the level of ob gene mRNA expression in retroperitoneal adipose tissue were significantly decreased after the feed induced obese rats were administrated with NPY Y5 receptor gene antisense oligodeoxynucleotide. There was significant difference in the above indexes in the antisense group when compared with those in the saline group and the mismatched group, except the difference in the wet weight of retroperitoneal adipose tissue between the antisense group and the mismatched group, which did not reach the statistical significance. Meanwhile, there was no significant difference in all of the observed indexes between the mismatched group and the saline group. Conclusion Intracerebroventricular injection of antisense oligodeoxynucleotide to neuropeptide Y Y5 receptor gene may improve the peripheral leptin resistance by decreasing the weight of retroperitoneal adipose tissue, the expression of ob gene and the levels of serum leptin and insulin in feed induced obese rats.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2002年第3期177-180,共4页
Chinese Journal of Endocrinology and Metabolism
基金
国家自然科学基金资助项目 (3 9870 3 62 )
江苏省教委自然科学基金资助项目 (98KJB3 2 0 0 0 2 )
