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目的:探讨神经肽YY5(NPYY5)受体反义基因治疗对肥胖大鼠高leptin血症的改善作用及其机制。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NPYY5受体反义、正义、错义寡核苷酸或生理盐水,观察大鼠腹膜后与生殖器周围脂肪组织湿重的变化,并采用ELISA双抗体夹心法测定血清leptin水平、放免法测定血清胰岛素水平。结果:①高营养饮食诱导的肥胖模型大鼠血清leptin水平、血清胰岛素水平及两部位脂肪组织湿重明显高于正常大鼠;②经NPYY5受体反义寡核苷酸干预后,肥胖大鼠血清leptin水平、血清胰岛素水平、腹膜后脂肪组织湿重均明显降低,但生殖器周围脂肪组织湿重无明显变化;③大鼠血清leptin水平、血清胰岛素水平、腹膜后脂肪组织湿重间均存在一定的正相关关系。结论:侧脑室注射NPYY5受体反义寡核苷酸可显著改善肥胖大鼠的高leptin血症,推测其机制可能与大鼠进食行为改变、腹膜后脂肪组织减少、血清胰岛素水平下降等因素有关。
Objective: To investigate the effect and mechanism of antisense neuropeptide YY5 (NPYY5) receptor therapy on obesity in rats with leptin hyperlipidemia. Methods: The model of obese rats induced by high nutritional diet was established. After intracerebroventricular injection of NPYY5 antisense, sense, missense oligonucleotide or normal saline, the wet weight of adipose tissue around the peritoneum and genitalia was observed The levels of leptin in serum were detected by ELISA double antibody sandwich method and serum insulin level was determined by radioimmunoassay. Results: ①Leptin level, serum insulin level and wet weight of adipose tissue in two obese rats induced by high nutrition diet were significantly higher than those in normal rats. ②After obesity was induced by NPYY5 receptor antisense oligonucleotide, Serum leptin level, serum insulin level, and weight of retroperitoneal adipose tissue were significantly decreased, but there was no significant change of wet weight of adipose tissue around genitals; ③Leptin level, serum insulin level and wet weight of retroperitoneal adipose tissue were both Positive correlation. Conclusion: Intracerebroventricular injection of NPYY5 receptor antisense oligonucleotide can significantly improve the high leptinmia in obese rats, suggesting that the mechanism may be related to changes in eating behavior, reduced retroperitoneal adipose tissue, serum insulin levels and other factors .