锰对小鼠脑基底核突触体谷氨酸和γ-氨基丁酸释放的影响

Effect of manganese on the release of glutamate and γ-aminobutyric acid in mouse basal nuclei synaptosomes

目的探讨锰对小鼠基底核突触体谷氨酸(Glu)和γ-氨基丁酸(GABA)释放的影响。方法将24只健康清洁级昆明小鼠按体重随机分为4组,分别为对照(生理盐水)组和25、50、100μmol/kg氯化锰染毒组,每组6只,雌雄各半。采用腹腔注射方式进行染毒,每周染毒5次,连续染毒4周。测量小鼠基底核内的锰含量;并用15 mmol/L KCl诱发并测定基底核突触体Glu和GABA的释放量。结果与对照组比较,50、100μmol/kg氯化锰染毒组小鼠基底核锰含量均增加,差异有统计学意义(P<0.05)。且随着锰染毒剂量的升高,小鼠基底核锰含量呈上升趋势。与对照组比较,25、50μmol/kg氯化锰染毒组小鼠基底核突触体Glu的释放量均增加,100μmol/kg氯化锰染毒组小鼠基底核突触体Glu的释放量及50、100μmol/kg氯化锰染毒组小鼠基底核突触体GABA的释放量均下降,差异有统计学意义(P<0.05);且随着氯化锰染毒剂量的升高,小鼠基底核突触体Glu释放量呈先上升后下降的趋势,而GABA释放量呈下降的趋势。结论锰可在小鼠脑基底核内蓄积,并对基底核突触体谷氨酸和GABA释放产生影响,造成神经系统紊乱。

Objective To study the effects of manganese （Mn） on the release of glutamate （Glu） and γ-aminobutyric acid （GABA） in mouse basal nuclei synaptosomes. Methods Twenty-four Kunming mice of clean grade were randomly divided into control, 25,50,100 p.mol/kg MnC12-exposed groups,six mice in each group,half male and half female. The mice were treated with 0.9% NaC1 and MnC12 through intraperitoneal injection,5 days per week,for four weeks. The levels of Mn in the basal nuclei were measured. Then,after synaptosomes were stimulated by 15 mmol/L KC1, Glu and GABA release were measured. Results Compared with the control group,the levels of Mn in basal nuclei of 50 and 100 μmol/kg body weight （BW） MnCI2 groups were significantly increased （P〈0.05）. With the increase of MnC12 dosage, the levels of Mn in mice basal nuclei were significantly increased,which indicated that Mn could accumulate in mouse brain through blood brain barrier. Compared with the control group,Glu release increased gradually in 25 μmol/kg and 50 μmol/kg BW Mn-exposed groups,but decreased in the 100 μmol/kg BW Mn-exposed groups. The GABA release decreased gradually in 50 and 100 μmol/kg BW Mn-exposed groups. There are no significantly different between male and female. Conclusion Manganese can accumulate in mouse basal ganglia and disturb the release of Glu and GABA in mouse basal nuclei synaptosomes, resulting in the central nervous system disorder.