一氧化氮合酶抑制剂对吗啡依赖大鼠睾丸细胞凋亡的影响

Effect of Nitric Oxide Synthase Inhibitor on the Testis Cell Apoptosis in Morphine-Dependent Rats

目的 :了解一氧化氮合酶 (NOS)抑制剂NG 硝基 左旋 精氨酸 (L NNA)对吗啡依赖纳洛酮催促戒断大鼠睾丸发育及其功能的影响 ,研究其对大鼠睾丸生精细胞凋亡的影响及其可能机制。 方法 :选用Wistar大鼠 4 8只 ,随机均分为对照组、戒断组和治疗组。以剂量递增法皮下注射吗啡建立吗啡成瘾大鼠模型 ,用纳洛酮催促戒断 ,测定戒断症状。采用放射免疫分析、原位缺口平移 (ISNT)和还原型尼克酰胺二磷酸腺苷脱氢酶 (NADPH d)组织化学等技术 ,观察大鼠睾丸钙调素 (CaM)含量、睾丸超氧化物歧化酶 (SOD)活性、还原型谷光甘肽过氧化物酶 (GSHPx)活性和睾丸凋亡细胞及其NOS阳性细胞的变化。 结果 :与对照组相比 ,吗啡依赖纳洛酮催促戒断组躯体运动神经功能和植物神经功能亢进 ,大鼠睾丸CaM含量减少 ,睾丸SOD、GSHPx活性降低 ,睾丸生精细胞凋亡和NOS阳性细胞数目明显增多 (P <0 .0 5或P <0 .0 1)。但L NNA对吗啡依赖大鼠的戒断症状及其睾丸NOS阳性细胞和凋亡细胞有明显的抑制作用 ,并可明显增加大鼠睾丸CaM ,SOD ,GSHPx的含量和活性。 结论 :吗啡依赖大鼠睾丸细胞凋亡明显增加 ,这种变化可能与睾丸NOS增加和CaM含量减少、睾丸SOD和GSHPx活性降低有关 ,但L NNA对其睾丸细胞凋亡及其相关生化指标有明显的保护作用。

Objective: To investigate the effect of N G-nitro-L-arginine(L-NNA), a nitric oxide synthase(NOS) inhibitor, on the testis cell apoptosis in morphine-dependent rats induced by naloxone and the involved mechanisms. Methods: Forty-eight Wistar rats were randomly divided into a control group, withdrawal group and a therapeutic group. Morphine-dependent rats were given gradually increasing doses of morphine to produce morphine-dependent models, the abstinent syndrome precipitated by naloxone. The inhibiting effect of L-NNA on the abstinent syndrome, and the testis apoptosis, NOS positive cells, calmodulin(CaM) contents, superoxide dismutase (SOD) activity, and glutathione superoxidase(GSHPx) activity of the morphine-dependent rats induced by naloxone were observed and recorded by radioimmunoassay, atomic absorption spectrometry, in situ nick translation(ISNT) and NADPH-d histochemical technique. Results: Compared with the control rats, the function of the somesthetic motor nerves and autonomic nerves was excessive, the apoptosis and NOS positive cells in the testis were significantly increased(P< 0.05 or P< 0.01), the content of CaM and the activity of SOD and GSHPx were obviously decreased in the morphine-dependent rats induced by naloxone. But L-NNA could significantly inhibit the abstinent syndrome, decrease NOS positive cells and apoptosis, and increase CaM content and the activity of SOD and GSHPx in the testis. Conclusion: Morphine dependence can induce testis cell apoptosis, an increase in testis NOS positive cells, a decrease in CaM content and the activity of SOD and GSHPx in the testis. L-NNA has the curative effect on the morphine abstinent syndrome, protects testis cells against apoptosis and improves their involved biochemical indexes.