School of Nursing, Jilin University, 965 Xinjiang Street, Changchun, Jilin Province, China.
Neurochem Int. 2011 Dec;59(8):1104-8. doi: 10.1016/j.neuint.2011.10.001. Epub 2011 Oct 10.
To explore the effects of heroin on purine nucleotides metabolism in rat brain.
Biochemical changes in association with heroin administration were compared between heroin-administered rats and non-heroin rats. HPLC method was used to detect the absolute content of purine nucleotides in brain tissues. Concentrations of uric acid (UA), blood urea nitrogen (BUN) and creatinine (Cre) in plasma were measured. Enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in brain tissue were analyzed. Real-time PCR was used to determine the relative level of transcripts of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT) and adenosine kinase (AK) in brain tissue.
Compared with those in the saline group, the content of AMP and GTP of heroin group decreased significantly; the UA concentration in plasma, ADA and XO activities and the mRNA level of ADA and XO in brain tissues in heroin group increased significantly; the mRNA level of AK, APRT and HGPRT in brain tissues in heroin group decreased significantly (P<0.01).
Heroin administration may enhance the catabolism and inhibit the anabolism of purine nucleotides in brain. There may be a deficiency of purine nucleotides, especially GTP and AMP in rat brain exposed to heroin. Our findings may provide a new potential approach to study the mechanism of heroin addiction.
探讨海洛因对大鼠脑嘌呤核苷酸代谢的影响。
比较海洛因给药大鼠与非海洛因大鼠的生化变化。采用 HPLC 法检测脑组织中嘌呤核苷酸的绝对含量。检测血浆中尿酸（UA）、血尿素氮（BUN）和肌酐（Cre）的浓度。分析脑组织中腺苷脱氨酶（ADA）和黄嘌呤氧化酶（XO）的酶活性。采用实时 PCR 法测定脑组织中 ADA、XO、腺嘌呤磷酸核糖转移酶（APRT）、次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）和腺苷激酶（AK）的转录物相对水平。
与生理盐水组相比，海洛因组 AMP 和 GTP 含量显著降低；海洛因组血浆中 UA 浓度、ADA 和 XO 活性以及脑组织中 ADA 和 XO 的 mRNA 水平显著升高；海洛因组脑组织中 AK、APRT 和 HGPRT 的 mRNA 水平显著降低（P<0.01）。
海洛因给药可能增强嘌呤核苷酸在脑内的分解代谢，抑制其合成代谢。海洛因暴露的大鼠脑组织可能存在嘌呤核苷酸，特别是 GTP 和 AMP 的缺乏。我们的发现可能为研究海洛因成瘾的机制提供一种新的潜在方法。
