海洛因及补偿嘌呤核苷酸对雄性大鼠生殖内分泌系统的影响

发布时间：2018-08-26 09:03

【摘要】： 海洛因等阿片类药物及毒品的滥用,会造成机体多个脏器、系统的毒性损害和潜在损害,生殖内分泌系统是海洛因损害的主要靶系统之一。本课题以雄性大鼠生殖内分泌系统为研究对象,从核苷酸代谢等多个新的方向研究了海洛因对雄性大鼠生殖内分泌系统的影响及补偿嘌呤核苷酸(AMP和GMP)的治疗作用。结果表明: 1.海洛因会引起HPG轴功能的失衡,其中对FSH的影响明显,对睾酮和LH的影响尚不显著,作用有一定持续性。嘌呤核苷酸补偿的各组大鼠血浆生殖激素水平相对稳定,提示嘌呤核苷酸补偿可能抑制海洛因对雄性大鼠HPG轴的不良影响。 2.未发现海洛因明显影响FSH和LH基因的表达。但与海洛因同时给嘌呤核苷酸、或海洛因撤药后给予嘌呤核苷酸则明显促进该基因的表达。 3.海洛因给药和停药均会影响ACTH的含量,且作用有持续性。嘌呤核苷酸补偿可以保持血浆ACTH含量的相对稳定。 4.海洛因使中性α-糖苷酶活性下降,并有持续性。嘌呤核苷酸的补偿可使中性α-糖苷酶含量保持相对稳定,提示嘌呤核苷酸的补偿可改善附睾的功能状态。 5.海洛因增强大鼠睾丸、附睾的嘌呤核苷酸分解代谢关键酶ADA的活性,且有一定持续性;同时补偿嘌呤核苷酸“对抗”了海洛因的作用。海洛因和补偿嘌呤核苷酸对睾丸、附睾和垂体补救合成关键酶HGPRT的影响有些不同。 6.海洛因给药有抑制大鼠睾丸、附睾组织内GDH和GS活性的趋势,使Glu含量有所增加。同时嘌呤核苷酸补偿或撤药会逆转海洛因对大鼠睾丸、附睾组织Glu代谢的影响。 7.海洛因对腺垂体促性腺细胞的超微结构造成损害,给予嘌呤核苷酸可以缓解或抑制海洛因的损害。总之,海洛因可引起机体生殖内分泌系统的变化,而这种变化在补偿嘌呤核苷酸后得以改善或拮抗。这种海洛因对机体生理功能及代谢的影响与嘌呤核苷酸代谢相关性的发现可能为阿片类物质依赖的机制研究和治疗开辟了新的方向。
[Abstract]:The abuse of opioid drugs such as heroin and drugs can cause many organs, systemic toxicity and potential damage. Reproductive endocrine system is one of the main target systems of heroin damage. The effects of heroin on reproductive endocrine system of male rats and the therapeutic effect of compensatory purine nucleotides (AMP and GMP) on the reproductive endocrine system of male rats were studied from several new directions such as nucleotide metabolism. The results show that: 1. Heroin can cause the imbalance of HPG axis function, among which the effect on FSH is obvious, but the effect on testosterone and LH is not significant. The plasma reproductive hormone level of rats compensated by purine nucleotides was relatively stable, suggesting that purine nucleotide compensation might inhibit the adverse effects of heroin on the HPG axis of male rats. 2. No significant effect of heroin on the expression of FSH and LH genes was found. However, purine nucleotides were given simultaneously with heroin, or purine nucleotides were given after withdrawal of heroin. Both heroin administration and withdrawal can affect the content of ACTH, and the effect is sustainable. Purine nucleotide compensation could maintain the relative stability of plasma ACTH content. 4. 4. Heroin decreased the activity of neutral 伪-glucosidase and sustained. The compensation of purine nucleotides can keep the content of neutral 伪 -glucosidase relatively stable, suggesting that the compensation of purine nucleotides can improve the functional state of epididymis. Heroin enhanced the activity of ADA, a key enzyme of purine nucleotide catabolism in rat testis and epididymis, and compensated purine nucleotides for "antagonizing" the effect of heroin. The effects of heroin and compensatory purine nucleotides on the key enzyme HGPRT of testicular, epididymal and pituitary biosynthesis were different. 6. 6. Heroin administration inhibited the activities of GDH and GS in testis and epididymis of rats and increased the content of Glu. At the same time, purine nucleotide compensation or withdrawal could reverse the effect of heroin on Glu metabolism in testis and epididymis of rats. Heroin caused damage to the ultrastructure of pituitary gonadotropin cells, and purine nucleotides could attenuate or inhibit the damage of heroin. In short, heroin causes changes in the body's reproductive endocrine system that are improved or antagonized by compensating purine nucleotides. The discovery of the correlation between the effects of heroin on physiological function and metabolism and the metabolism of purine nucleotides may open a new direction for the study and treatment of opioid dependence.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R363;R96

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