嘌呤核苷酸对海洛因依赖及戒断大鼠垂体嘌呤核苷酸代谢关键酶基因表达的影响

Effect of purine nucleotide on gene expression of key enzymes to purine nucleotide metabolism of pituitary in heroin addicted and withdrawal rats

目的研究嘌呤核苷酸对海洛因依赖及戒断大鼠垂体嘌呤核苷酸分解代谢关键酶腺苷脱氨酶(ADA)、嘌呤核苷酸补救合成关键酶次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT)基因表达的影响,阐明海洛因对垂体嘌呤核苷酸代谢的损害及嘌呤核苷酸补偿的对抗作用。方法建立海洛因依赖及戒断大鼠模型,80只建模成功的雄性Wistar大鼠随机分成对照组(生理盐水)、核苷酸组(不给海洛因)、海洛因组、海洛因+核苷酸组(同时给药)、海洛因戒断3d组、海洛因戒断9d组、核苷酸3d组(海洛因停药后给核苷酸3d)及核苷酸9d组(海洛因停药后给核苷酸9d)(每组10只)。检测垂体组织内ADA及HGPRT基因表达的情况。结果与对照组比较,海洛因组、戒断3d组大鼠垂体ADA mRNA水平有所增高,但差异均无显著性(P>0.05)。垂体组织核苷酸组HGPRT mRNA水平高于对照组(P<0.05),其他各组与对照组比较,差异均无显著性(P>0.05)。结论海洛因有增强大鼠垂体组织ADA基因表达,减弱HGPRT的基因表达作用,但作用不显著;补偿嘌呤核苷酸保持海洛因依赖大鼠垂体ADA和HGPRT基因表达的相对稳定。

Objective Opioid abuse is a important problem in the world.As one of opioid,heroin can damage many organs of body severely.Previous study in our lab indicated that heroin can enhance catabolism of purine nucleotide of rats,and the abnormality of many biochemical indicators can be reverse or release when adenosine or purine nucleotide were given at the same time.There is few studies about gene expression of adenosine deaminase（ADA） and hypoxanthine-guanine phosphoribosyl transferase（HGPRT） of pituitary.Objective：To investigate the effect of purine nucleotide on the gene expression of ADA and HGPRT of pituitary in the heroin dependence and withdrawal rats.Methods The rat models of heroin dependence and withdrawal were set up.80 male Wistar rats were randomly divided into 8 groups（10 rats of each group）：control（C）,nucleotide group（N）,heroin administration group（H）,heroin and nucleotide group（HN）,3d withdrawal group（W3）,9d withdrawal group（W9）,nucleotide 3d group（N3）,nucleotide 9d group（N9）.Adenosine deaminase and hypoxanthine-guanine phosphoribosyl transferase gene expression in pituitary of rats in various group rats were detected.Results Compared with control group,the ADA mRNA levels in heroin administration group,3d withdrawal group of pituitary increased,but the difference was no significant（P0.05）.The HGPRT mRNA pituitary levels in nucleotide group of pituitary higher than that in control group（P0.05）.And compared with the control group,no significant difference in the other groups（P0.05）.Conclusion Heroin enhance the gene expression of adenosine deaminase and weaken the gene expression of hypoxanthine-guanine phosphoribosyl transferase in pituitary of rats,but the effect is not obviously.Purine nucleotide compensation can maintain the gene expression of ADA and HGPRT in a stable situation.