电针对氯胺酮成瘾大鼠内侧前额叶皮质酪氨酸羟化酶表达的影响

Effects of electroacupuncture intervention at different times of a day on expression of tyrosine hydroxylase in medial prefrontal cortex of rats with ketamine addiction

目的观察不同时辰电针"足三里"和"三阴交"穴对氯胺酮成瘾大鼠内侧前额叶皮质(mPFC)酪氨酸羟化酶(TH)表达的影响,探讨电针治疗氯胺酮滥用成瘾的作用机制。方法将56只SD大鼠随机分为正常对照组、生理盐水对照组、模型组、电针治疗组,电针治疗组再分为子时(23:00)、卯时(05:00)、午时(11:00)、酉时(17:00)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,不同时辰电针组在给药7d后分别选取一侧"足三里"和"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mPFC内TH的表达。结果与正常对照组和生理盐水对照组相比较,模型组mPFC内TH免疫反应阳性神经元的数量明显增多(P<0.01),细胞平均灰度值降低(P<0.01),与模型组相比较,午时、酉时电针组TH免疫反应阳性神经元的数量明显减少(P<0.01),细胞平均灰度值升高(P<0.01);子时、卯时电针组则无明显变化(P>0.05)。结论氯胺酮成瘾使mPFC内TH的表达明显增加;午时、酉时电针"足三里"和"三阴交"穴可明显下调mPFC内TH的表达,改善氯胺酮成瘾症状。

Objective To explore the role of different time points of electroacupuncture （EA） at ＂Zusanli＂ （ST36） and ＂Sanyinjiao＂ （SP6） on treatment of ketamine addiction by observing the cognitive- improving effect and the expression of tyrosine hydroxylase （TH） immunoreaction （IR） positive neurons in the medial prefrontal cortex（mPFC）. Methods A total of 56 Sprague-Dawley rats were randomized into normal control group, normal saline group （10ml/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 estah[ished by intraperitoncal administration of ketamine （100 mg/kg）, once a day for 7 days. EA （2Hz,3v） was applied to unilateral ＂Zusanli＂ （ST36） and ＂Sanyinjiao＂ （SP6） for 30min, once daily for 7 days. The expression of TH in mPFC was detected by immunohistochemistry. Results Compared with those of the normal control and normal saline groups, the number of TH IR-positive neu rons in mPFC of the model group was upregulated significantly （P〈0.01）, and the average gray value downregulated significantly （P〈0.01）. Compared with that of the model group, the expression of TH IR-positive neurons was downregulated significantly in the Wu-Shi （11. 00） and You-Shi （17： 00） subgroups （P〈0.01）, rather than in the Zi-Shi （23.00） and Mao-Shi （05：00） subgroups （P〈0.05）. Conclusion EA of ＂Zusanli＂ （ST36） and ＂Sanyinjiao＂ （SP6） at 11.00 and 17：00 of the daytime can down- regulate the increase of expression of TH in mPFC of ketamine addiction rats, which may contribute to its clinical effect in relieving ketamine addiction symptoms.