不同时辰电针对氯胺酮成瘾大鼠伏隔核神经元型一氧化氮合酶表达的影响

Effects of electroacupuncture on the expression of nNOS in nucleus accumbens septum in ketamine addiction rats

目的: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大鼠随机分为正常对照组、生理盐水对照组、模型组、子时电针组、卯时电针组、午时电针组、酉时电针组,每组8只。后5组造模,每日腹腔注射氯胺酮100mg/kg,连续7d。各电针治疗组在氯胺酮给药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)两侧交替进行电针治疗,每日治疗1次,每次30min,连续治疗7d;生理盐水对照组每日给予生理盐水10ml/kg,连续7d。正常对照组不予干预处理。采用免疫组织化学染色方法显示伏隔核(NAc)不同亚区—核部(NACc)和壳部(NACsh)神经元型一氧化氮合酶(nNOS)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NACc和NACsh中的nNOS阳性神经元的表达明显增加(均P<0.01)。与模型组相比较,午时、酉时电针组NACc和NACsh中的nNOS阳性神经元的表达明显减少(均P<0.01),子时、卯时电针组则均无明显变化(均P>0.05)。结论:午时、酉时电针"足三里"与"三阴交"穴可明显下调氯胺酮成瘾增加的NACc和NACsh中的nNOS的表达,提示电针可能通过调节NAc的神经元活动改善氯胺酮成瘾。

Objective To explore the possible mechanism of electroacupuncture （EA） at different time in treatment of ketamine addiction. Methods Fifty six Sprague-Dawley rats were randomized into a normal control group, a normal saline group, a model group, a Zishi （ 23 ： 00 - 1 ： 00） EA group, a Maoshi （ 5 ： 00 - 7 ： 00 ） EA group, a Wushi （ 11 ： 00- 13 ： 00） EA group and a Youshi （ 17 ： 00 - 19 ： 00 ） group, 8 rats in each group. The rat model was estahlished in the latter five groups by intraperitoneal administration of ketamine （100 mg/kg）, once a day for 7 days. One week after injecting, EA （2 Hz） was applied to the EA groups ahernatively on each side ot ＂Zusanli＂ （ST 36） and ＂Sanyinjiao＂ （SP 6） for 30 min at different time, once a day for 7 days, the normal saline group was treated by intraperitoneal of normal saline （10 ml/kg） for 7 days, the normal control group received no treatment. The expression of neuronal nitric oxide synthase （nNOS） in the different subregion of Nucleus accum bens septum （NAC）, ie. , core （NACc） and shell （NACsh）, was detected by immunohistochemistry. Results Compared with the normal control group and normal saline group, the expression of nNOS positive neurons in NACc and NACsh in the model group were increased significantly （all P〈0.01）. After Wushi EA and Youshi EA, the expression of nNOS positive neurons in NACc and NACsh were significantly lower than that in model group （both P〈0. 01）, but Zishi EA and Maoshl EA groups had no obvious difference（both P）〉0. 05）. Conculsion EA at＂Zusanli＂ （ST 36） and＂Sanyinjiao＂ （SP 6） duringWushi （11：00-13：00） andYoushi （17：00 -19：00） can downregulate the expression of nNOS in NACc and NACsh induced by ketamine addiction, which indicates that EA may contribute to regulate the activity of NAC neurons so as to alleviate ketamine addiction.