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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温重的变化 ,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、腹膜后脂肪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、腹膜后脂肪组织温重均明显降低 ,但生殖器周围脂肪组织温重无明显变化 ;③大鼠血清Leption水平、血清胰岛素水平、腹膜后脂肪组织温重间均存在一定的正相关关系。结论 :侧腔室注射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 high Leptin. Methods: The model of obesity induced by high nutritional diet was established. After intracerebroventricular cannulation, NPYY5 receptor antisense, sense, missense oligonucleotide or saline were injected to observe the effects of intraperitoneal The level of serum leptin was measured by ELISA double antibody sandwich method, and the level of serum insulin was determined by radioimmunoassay. Results: ①Leptin level, serum insulin level and wet weight of retroperitoneal fat in obesity model induced by high nutrition diet were significantly higher than those in normal rats. ② After intervention with NPYY5 receptor antisense oligonucleotide, Leptin level, serum insulin level and weight of retroperitoneal adipose tissue were significantly decreased, but there was no significant change in the temperature and weight of adipose tissue around genitalia. ③ There was a positive correlation between serum leptin level, serum insulin level and weight of retroperitoneal adipose tissue relationship. CONCLUSION: Injection of NPYY5 receptor antisense oligonucleotide into the lateral chamber can significantly improve the high Leptinmia in obese rats. It is presumed that the mechanism may be related to the change of feeding behavior, the decrease of retroperitoneal adipose tissue and the decrease of serum insulin related