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司来吉兰对帕金森病模型大鼠胃窦酪氨酸羟化酶和神经元型一氧化氮合酶表达的影响
毕树立1,2,刘斌1*,高海英3
0
(1. 河北联合大学附属医院神经内一科, 唐山 063000;
2. 唐山市开平区医院急诊科, 唐山 063021;
3. 唐山市丰南区医院神经内科, 唐山 063300
*通信作者)
摘要:
目的 观察司来吉兰对帕金森病(Parkinson disease,PD)模型大鼠胃功能障碍及胃窦酪氨酸羟化酶(tyrosine hydroxylase,TH)及神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)表达的影响,探讨司来吉兰对PD胃功能障碍的治疗作用及可能机制。方法 72只健康SD大鼠随机分为正常对照组、PD模型组和司来吉兰治疗组,后两组采用颈背部皮下注射鱼藤酮制备PD模型,模型制备成功后,模型组每日并灌胃生理盐水,治疗组每日灌胃给药司来吉兰0.5 mg/kg。分别于治疗后4 d、8 d测定胃固体食物残留率,并采用免疫组化法和蛋白质印迹法检测胃窦TH和nNOS的表达。结果 与对照组相比,模型组各时间点胃内固体食物残留率均增加,胃窦TH表达均减少,nNOS表达均增加,差异有统计学意义(P<0.01)。与模型组相比,治疗组各时间点胃内固体食物残留率均降低,胃窦TH表达均升高,nNOS表达均降低,差异有统计学意义(P<0.05或P<0.01)。与治疗4 d组相比,治疗8 d组大鼠胃内固体食物残留率明显降低,TH表达明显升高, nNOS阳性细胞表达明显降低,差异均有统计学意义(P<0.05)。结论 司来吉兰可改善PD大鼠胃功能障碍,其作用机制可能与其减轻PD模型大鼠胃窦多巴胺能神经元的损伤和抑制nNOS表达有关。
关键词:  帕金森病  酪氨酸羟化酶  一氧化氮合酶  胃窦  司来吉兰
DOI:10.3724/SP.J.1008.2014.01197
投稿时间:2014-05-11修订日期:2014-09-25
基金项目:唐山市科学技术研究与发展指导计划(13130292a).
Effects of selegiline on tyrosine hydroxylase and neuronal nitric oxide synthase in gastric antrum of rats with Parkinson disease
BI Shu-li1,2,LIU Bin1*,GAO Hai-ying3
(1. First Department of Neurology, the Affiliated Hospital of Hebei United University, Tangshan 063000, Hebei, China;
2. Department of Emergency, Hospital of Kaiping District, Tangshan 063021, Hebei, China;
3. Department of Neurology, Hospital of Fengnan District, Tangshan 063300, Hebei, China
*Corresponding authors)
Abstract:
Objective To observe the effects of selegiline on tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) in the gastric antrum of rats with Parkinson disease(PD), so as to investigate the therapeutic effect and mechanism of selegiline for treatment of gastric disfunction in PD. Methods A total of 72 SD rats were randomly divided into normal control group, PD model group, and selegiline treatment group. PD rat models were established by subcutaneous rotenone injection. After the success of model preparation, PD group was given normal saline, and the therapy group was given selegiline (0.5 mg/kg) by intragastric administration. At 4 d and 8 d after therapy, residual rate of solid food was detected in the stomachs of animals, and the expressions of TH and nNOS were detected by immunohistochemistry method and Western blotting analysis. Results Compared with the control group, the model group had significantly higher residual rate of solid food, significantly lower TH expression, and significantly increased nNOS expression in the gastric antrum (all P<0.01). Compared with the model group, the treatment group had significantly decreased residual rate of solid food, significantly increased TH expression and significantly lower nNOS expression in the gastric antrum at all time points(P<0.05,or P<0.01). At 8 days after selegiline treatment, the residual rate of solid food was significantly lower, TH expression was significantly increased, and nNOS expression was significantly decreased (all P<0.05) compared with those at 4 days after treatment. Conclusion Selegiline can improve the gastric dysfunction in PD rats, which might be related to relieve of gastric dopaminergic neuronal injury and inhibition of nNOS expression.
Key words:  Parkinson disease  tyrosine hydroxylase  nitric oxide synthase  castric antrum  selegiline