二巯丙磺钠对四次甲基二砜四胺拮抗GABA受体的影响

摘要

目的：探讨二巯丙磺钠(DMPS)对四次甲基二砜四胺(TETS)拮抗GABA受体的影响.方法：通过急性毒性试验观察DMPS和TETS对小鼠的影响；利用氨基酸自动分析仪测定小鼠脑内游离氨基酸的变化；通过宏观放射自显影术观察不同实验组中[3H]-GABA与其受体结合情况.结果：与NS对照组比较，icv和ip DMPS后小鼠的惊厥数从20只下降至4只和2只；小鼠脑内游离GABA含量与DMPS保护组和生理盐水组比较，DMPS对照组和TETS对照组含量均有变化[μmol/g：(2.09±0.05)和(2.67±0.15)，vs(2.40±0.10)和(2.41±0.21)];在NS对照组、DMPS对照组、TETS对照组和DMPS保护组中，小鼠脑内游离的谷氨酸(Glu)含量分别是(12.3±1.2)，(12.0±0.8)，(10.2±0.6)和(11.8±1.0)μmol/g.与缓冲液对照组大鼠脑片中不同脑区[(0.102±0.003)，(0.109±0.005)，(0.128±0.007)和(0.125±0.008)]比较，TETS组放射自显影图像中大脑皮质、海马、间脑、脑干的光密度显著降低[(0.084±0.008)，(0.081±0.009)，(0.094±0.006)，和(0.081±0.006)]; DMPS+TETS组中不同脑区的光密度[(0.116±0.008)，(0.125±0.011)，(0.129±0.005)和(0.128±0.010)]维持或高于正常水平[(0.102±0.003)，(0.109±0.005)，(0.128±0.007)和(0.125±0.008)].结论：DMPS通过增加脑内GABA与受体的结合发挥抑制TETS拮抗GA-BA受体的作用.%AIM: To study effects of sodium dimercaptopropanesulfonate (DMPS) on the antagonism of tetramethylenedisulphotetramine (TETS) to y-aminobutyric acid (GABA) receptor. METHODS: Acute toxicity experiments were conducted to observe the effects of DMPS and TETS on mice. Contents of free amino acids in mouse brain were determined with automatic analyzer for amino acids. Autoradiography was used to observe the [3H]GABA bindings in the rat brain slices under different conditions. RESULTS: After icv and ip DMPS, the number of mice experiencing convulsions reduced from 20 in control group to 4 and 2 respectively in TETS poisoned mice. The content of GABA was altered in DMPS control group and TETS control group compared with DMPS protection group and NS control group [μmoL/g: (2.09±0.05) and (2.67±0.15) vs (2.40±0.10 (μmol/g) ) and (2.41 ± 0.21 ) ]; the content of glutamic acid was (12.3±1.2), (12.0±0.8) , (10.2±0.6), and (11.8± 1.0) μmol/g in NS control group, DMPS control group, TETS control group, and DMPS protection group, respectively. The OD value of autoradiograms decreased in TETS group compared with buffer control group in cortex, hippocampus, diencephalon, and brainstem [(0.084 ± 0.008), (0.081 ± 0.009), (0.094 ±0.006) and (0.081 ± 0.006), vs (0.102 ± 0.003),(0.109 ± 0.005), (0.128 ± 0.007), and (0.125 ±0.008), respectively ]. OD value was maintained or higher than the normal level in DMPS + TETS group in the four brain areas [(0.116 ± 0.008), (0.125 ±0.011), (0.129 ± 0.005), and (0.128 ± 0.010) vs (0.102±0.003), (0.109±0.005), (0.128±0.007),and (0.125 ± 0.008), respectively]. CONCLUSION:The inhibitory effects of DMPS on the antagonism of TETS to GABA receptor are due to the increase in the GABA binding to its receptors in brain caused by DMPS.