肠道植物乳杆菌细胞外囊泡对酒精依赖大鼠酒精偏好调控作用

Effects of extracellular vesicles of intestinal Lactobacillus plantarum on alcohol preference in alcoholdependentrats

目的 研究植物乳杆菌来源的细胞外囊泡(L-EVs)对酒精依赖大鼠酒精偏好的影响,为酒精依赖的临床治疗及预防提供理论依据。方法 SD雄性大鼠(180~200g)利用慢性间歇性主动饮酒(IA2BC)方法建立大鼠酒精依赖模型。当建模21d时,随机将饮酒大鼠分为腹腔注射组和中脑腹侧背盖区(VTA)注射组,VTA注射组给予脑立体定位术在VTA留置套管,继续完成28d建模;建模成功后测量大鼠戒断0h、72h后再饮酒时酒精偏好。在酒精戒断期间向大鼠腹腔或者直接VTA注射L-EVs,测量给药后大鼠的酒精偏好,部分大鼠预先在VTA注射原肌球蛋白受体激酶B(TrkB)的拮抗剂K252a。结果 腹腔注射L-EVs后,与戒断组和溶剂组相比,SD大鼠的酒精偏好明显降低(P<0.01),VTA中微量注射L-EVs后,与假手术组和溶剂组相比,SD大鼠酒精偏好均明显降低(P<0.01),而在L-EVs注射前预先注射K252a可以拮抗L-EVs对酒精依赖大鼠酒精偏好的抑制作用。注射L-EVs与向VTA注射脑源性神经营养因子(BDNF)对酒精依赖大鼠戒断后再饮酒时饮酒偏好的影响是相似的。并且,腹腔注射L-EVs可以增加酒精依赖大鼠VTA BDNF的表达。结论 植物乳杆菌来源的EVs可能通过BDNF发挥对酒精依赖大鼠的酒精偏好调节作用。

Objective To investigate the effects of lactobacillus plantarum-derived extracellular vesicles(L-EVs)on alcohol preference in alcohol-dependent rats,and to provide a theoretical basis for the clinical treatment and prevention of alcohol dependence.Methods SD male rats(180-200g)were used to establish a rat alcohol dependence model using the chronic intermittent active drinking(IA2BC)method.When modelling was done at 21 d,the drinking rats were randomly divided into an intraperitoneal injection group and a midbrain ventral dorsal cap area(VTA)injection group,and the VTA injection group was given a brain stereotaxic placement of a cannula in the VTA and continued to complete modelling for 28 d.After successful modelling,alcohol preference was measured when the rats drank again after Oh and 72h of abstinence.Alcohol preference was measured after administration of L-EVs to rats during alcohol withdrawal,either intraperitoneally or directly into the VTA,and some rats were pre-injected with K252a,an antagonist of pro-myosin receptor kinase B(TrkB),in the VTA.Results Alcohol preference was significantly lower in SD rats after intraperitoneal injection of L-EVs compared to the withdrawal and solvent groups(P<0.01),and in the VTA After microinjection of L-EVs,alcohol preference was significantly lower in SD rats compared with both the sham-operated and solvent groups(P<0.01),whereas pre-injection of K252a prior to L-EVs injection antagonized the inhibitory effect of L-EVs on alcohol preference in alcohol-dependent rats.The effects of injecting L-EVs and injecting brain-derived neurotrophic factor(BDNF)into the VTA on drinking preference in alcohol-dependent rats when drinking again after withdrawal were similar.Moreover,intraperitoneal injection of L-EVs increased the expression of BDNF in the VTA of alcohol-dependent rats.Conclusions Lactobacillus plantarum-derived EVs may exert a modulatory effect on alcohol preference in alcohol-dependent rats via BDNF.