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目的:研究一氧化氮合酶抑制剂N硝基L精氨酸对海洛因依赖性大鼠催促后出现的戒断综合征的治疗效果。方法:采用剂量递增法,皮下注射海洛因从1mg·kg-1增至8mg·kg-1,并维持该剂量至42d,经纳洛酮催促后得到理想的大鼠海洛因依赖模型。在该模型的基础上选用3,9,18,27mg·kg-14种N硝基L精氨酸剂量给雄性大鼠灌胃。结果:发现4个剂量组与自然戒断组比较,经t检验后均有统计学意义。27mg·kg-1的剂量组与自然戒断组评分比较有极显著性差异(P<0.01),其余3个剂量组与自然戒断组评分比较差异有显著性(P<0.05)。实验结果还发现,催促戒断的雄性大鼠在27mg·kg-1NLArg的保护下,其腹泻症状和激惹症状与自然戒断组差异有显著性,分别为P<0.01和P<0.05。血清中NO、皮质醇和超氧化物歧化酶(SOD)活性测定结果显示:NOS抑制剂1,2mg·kg-1可明显降低NO含量,而4mg·kg-1·d-1无作用;长期使用NOS抑制剂N硝基L精氨酸,SOD的活性升高,但各组间的皮质醇含量无明显差异。结论:实验结果表明,N硝基L精氨酸对海洛因戒断综合征有明显的治疗作用,且呈剂量相关趋势,尤其对大鼠的腹泻和激惹症状有很好的疗效
Objective: To investigate the therapeutic effect of nitric oxide synthase inhibitor N-nitro-L-arginine on withdrawal syndrome after heroin-dependent rats’ urging. Methods: The dosage of heroin was increased from subcutaneous injection of 1 mg · kg-1 to 8 mg · kg-1 and the dosage was maintained till 42 days. The ideal rat model of heroin dependence was obtained after naloxone stimulation. On the basis of the model, 3, 9, 18, 27 mg · kg-14 N-nitro-L-arginine doses were administered intragastrically to male rats. Results: Compared with the natural withdrawal group, the four dose groups were found to have statistical significance after t test. 27mg · kg-1 dose group compared with the natural withdrawal group score had significant difference (P <0.01), the other three dose group and natural withdrawal group score difference was significant (P <0.05). The experimental results also found that the withdrawal of male rats in the protection of 27mg · kg-1NLArg diarrhea and irritability symptoms and natural withdrawal group differences were significant, respectively P <0.01 and P <0.05. Serum NO, cortisol and superoxide dismutase (SOD) activity measurement results showed that: NOS inhibitor 1, 2mg · kg-1 can significantly reduce the NO content, while 4mg · kg-1 · d-1 no effect; long-term use NOS inhibitor N nitro L arginine, SOD activity increased, but the cortisol content between the groups no significant difference. CONCLUSIONS: The experimental results show that N-nitro-L-arginine has a significant therapeutic effect on heroin withdrawal syndrome and shows dose-related trends, especially for the treatment of diarrhea and irritation symptoms in rats