摘要
目的:探讨神经肽Y-Y5受体反义基因治疗后正常SD大鼠减肥减重效应与外周白色脂肪细胞体积、数目变化的关系。方法:侧脑室插管,注射针对Y5受体编码起始区的反义、正义、错义寡聚脱氧核糖核酸及生理盐水,采用MPLAS-500多媒体彩色病理图文分析系统计算平均脂肪细胞面积,基因组DNA提取物凝胶电泳检测脂肪细胞凋亡,RT-PCR分析凋亡相关基因Bcl-2、Bax表达的改变。结果:①Y5受体反义基因治疗后大鼠进食量与体重显著降低,外周白色脂肪组织湿重与平均脂肪细胞面积明显减少;②脂肪组织基因组DNA提取物凝胶电泳出现凋亡特征性梯状条带;③凋亡相关基因Bcl-2表达下调、Bax表达上调。结论:平均脂肪细胞面积减小、脂肪细胞凋亡增加可能是Y5受体反义基因治疗减肥减重的重要原因。
Objective: To investigate the influence of central administration ofneuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs) on body weight, fat pads of SDrats, and the effects of white adipocytes lipolysis and apoptosis. Methods: Y5 receptor antisense,sense, mismatched ODNs or vehicle was intracerebroventricularly (i. c. v.) injected. Averageadipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCRwas used to analyse the expression of Bcl-2 and Bax gene. Results: Central administration of Y5antisense ODNs significantly decreased body weight, and average adipocyte area. DNA fragmentationwas present after electrophoresis at epididymal adipose tissue. The expression of Bcl-2 gene wasdownregulated, while the expression of Bax upregulated. Conclusion: Lipolysis and adipocyteapoptosis may be important mechanisms far 75 antisense therapy.
基金
Supported by grant from National Natural Science Foundation (39870362)
Natural Science Foundation of Education Committee of Jiangsu Province (98KJB320002).
