高频电刺激伏隔核对肥胖大鼠摄食量的影响及其机制研究

Effects of high frequency stimulation of nucleus accumbens on food intake in obesity rats and its mechanism

目的探索伏隔核（NAc）脑深部电刺激（DBS）对肥胖大鼠摄食量和NAc多巴胺受体表达水平的影响，为揭示NAc—DBS调控摄食行为的中枢机制提供依据。方法40只大鼠利用高脂饮食诱导肥胖模型，将成功建模的36只大鼠随机均分核部组和壳部组，分别在NAc的核部和壳部植入刺激电极固定装置，成功植入的大鼠共32只（核部组和壳部组分别16只）。每组再随机均分为两个亚组，即DBS组与假刺激组，对DBS组给予连续高频电刺激7d，假刺激组不刺激。观察在此期间各组大鼠的摄食量和摄水量的变化，并利用实时定量PCR技术检测NAc核部与壳部D1和D2受体的表达水平。结果NAc壳部DBS组大鼠摄食量从第5天开始与假刺激组比较差异有统计学意义（P〈0．05），且其D2受体表达较假刺激组上调（P〈0．05），而NAc核部电刺激对肥胖大鼠摄食量及D2受体表达影响差异无统计学意义。高频电刺激对肥胖大鼠的摄水量及D1受体表达影响差异无统计学意义。结论。高频电刺激能有效降低肥胖大鼠摄食量，有效刺激靶点为NAc壳部而非核部；具体机制可能与D2受体表达上调有关。

Objective To explore the effects of chronic high frequency deep brain stimulation （DBS） of accumben nucleus on food intake and expression of dopamine D1 and D2 receptors and provide evidence for the central mechanism of the effects. Methods 40 rats received high - fat diet to induce obesity and 36 reached the standard of obesity. These rats were randomly even divided in two groups, namely core group and shell group. Stimulating electrode was implanted in the corresponding target. Thirty - two rats survived and were further evenly divided into DBS subgroup and sham DBS subgroup. Rats in the DBS subgroup received continuous high frequency DBS for 7 days. The amount of food and water intake was measured during the period. Seven days later,the rats of all groups were sacrificed to obtain the brain tissue in accumbens nucleus shell and core subregion. The levels of D1 and D2 cDNA were measured using quantitative real time PCR to observe the effect of accumbens nucleus chronic high frequency stimulation on the D1 and D2 receptors expression. Results The amount of food intake began to show significant difference between the NAc shell DBS and sham DBS subgroups from the 5th day （ P 〈 0. 05 ）. D2 receptor expression was downregnlated after 7 days of DBS in the NAc shell group. However,no difference was shown between the NAc core DBS and sham DBS subgroups. The amount of water intake showed no significant difference among the four subgroups. Conclusion The effective target region of high frequency stimulation to decrease the amount of food intake is the NAc shell subregion rather than core subregion. The mechanism involved might be due to upregulation of D2 receptor in the NAc shell subregion.