不同时辰电针对氯胺酮成瘾大鼠伏隔核酪氨酸羟化酶及c-fos表达的影响

Effects of Electroacupuncture Intervention at Different Time in A Day on Expression of Tyrosine Hydroxylase and c-fos in Nucleus Accumbens in Ketamine Addiction Rats

目的:观察不同时辰电针对氯胺酮成瘾大鼠伏隔核酪氨酸羟化酶(TH)及c-fos表达的影响,探讨不同时辰电针对氯胺酮成瘾大鼠戒毒治疗的可能机制。方法:将56只SD大鼠随机分为正常组、生理盐水组、模型组、不同时辰电针组(分23:00子时、05:00卯时、11:00午时、17:00酉时4个电针组),每组8只。每天1次经腹腔注射氯胺酮复制氯胺酮成瘾模型,不同时辰电针组于给药1周后分别在4个时辰选取一侧"足三里"与"三阴交"穴给予低频(2Hz)电针治疗,每次30min,连续治疗7d。采用免疫组织化学染色方法检测伏隔核TH及c-fos的表达。结果:与正常组和生理盐水组相比较,模型组TH及c-fos免疫反应阳性神经元的数目明显增多(P<0.01)。与模型组相比较,午时、酉时电针组TH及c-fos免疫反应阳性神经元的数目明显减少(P<0.01),而子时、卯时电针组则无明显变化(P>0.05)。结论:电针"足三里"与"三阴交"可明显抑制氯胺酮成瘾引起的伏隔核TH及c-fos表达的增强,提示电针可能通过抑制伏隔核多巴胺神经元的活动改善氯胺酮成瘾,但不同时辰针刺疗效存在差异。

Objective To observe the effect of electroacupuncture（EA） intervention at different time in a day on the expression of tyrosine hydroxylase（TH） and c-fos in the Nucleus Accumbens（NAc） so as to explore its mechanism underlying improvement of ketamine addiction.Methods A total of 56 Sprague-Dawley rats were randomized into normal control,normal saline（2 mL/kg）,model and EA groups.The EA group was subdivided into Zi-Shi（23：00）,Mao-Shi（05：00）,Wu-Shi（11：00） and You-Shi（17：00） subgroups.Ketamine addiction model was established by intraperitoneal administration of ketamine（100 mg/kg）,once a day for 7 days.EA（2 Hz,3 V） was applied to unilateral ＂Zusanli＂（ST 36） and ＂Sanyinjiao＂（SP 6） for 30 min,once daily for 7 days.The expression of TH and c-fos in the NAc was detected by immunohistochemistry.Results Compared with the normal control group and normal saline group,the numbers of TH and c-fos immunoreaction（IR）-positive neurons in NAc in the model group were upregulated significantly（P0.01）.Compared with the model group,the expression levels of both TH and c-fos IR-positive neurons were down-regulated significantly in the Wu-Shi（11：00） and You-Shi（17：00） subgroups（P0.01）,rather than in the Zi-Shi and Mao-Shi subgroups（P0.05）.Conculsion EA of ＂Zusanli＂（ST 36） and ＂Sanyinjiao＂（SP 6） at 11：00 and 17：00 of the daytime can down-regulate ketamine addiction induced increase of expression of TH and c-fos in the NAc in ketamine addiction rats,which may contribute to its effect in relieving ketamine addiction symptoms in clinic.