二巯丙磺钠对溴苯腈急性中毒小鼠中枢神经毒性作用的干预

目的 研究溴苯腈急性染毒对小鼠大脑皮层中γ-氨基丁酸(GABA)和谷氨酸(Glu)含量等指标的影响及二巯丙磺钠(Na-DMPS)的作用.方法 将30只ICR小鼠(雌雄各半)随机分成对照组和染毒组,每组10只.对照组予体积分数为10%的DMSO溶液(20ml/kg)灌胃;染毒组予溴苯腈(200mg/kg)灌胃染毒;Na-DMPS保护组予溴苯腈(200mg/kg)灌胃染毒后,即刻以Na-DMPS(300mg/kg)腹腔注射.观察6 h后处死,采用反相高效液相色谱法测定各组小鼠大脑皮层中GABA、Glu含量,同时采用紫外分光光度计比色法等方法测定大脑皮层中谷氨酰胺(Gln)含量及谷氨酰胺合成酶(GS)、谷氨酸脱羧酶(GAD)、γ-氨基丁酸转氨酶(GABA-T)的活力.结果 与对照组GABA为(3.41±0.12)μmol/g、Glu为(14.00±0.16)μmol/g、Gln为(1.25±0.19)μmol/g、GAD为(13.50±0.25)μmol·g-1·h-1、GABA-T为(25.51±0.21)μmol·g-1·h-1、GS为(142.19±1.31)U/mgpro]比较,急性中毒组小鼠大脑皮层GABA(3.14±0.14)μmol/g]含量降低,Glu(17.54±0.40)μmol/g]和Gln(3.35±0.27)μmol/g]含量增高,GAD(11.93±0.15)μmol·g-1·h-1]、GABA-T(24.15±0.22)μmol·g-1·h-1]、GS(140.75±1.01)U/mg pro]活力下降,差异均有统计学意义(P＜0.05);与急性中毒组相比,Na-DMPS组GABA(3.52±0.30)μmol/g]含量升高,Glu(14.20±0.32)μmol/g]和Gln(1.32±0.17)μmol/g]含量降低,GAD(13.01±0.45)μmol·g-1·h-1]、GABA-T(25.19±0.26)μmol·g-1·h-1]、GS(142.35±1.20)U/mgpro]活力增强,差异均有统计学意义(P＜0.05);Na-DMPS保护组与对照组相比,大脑皮层中GABA、Glu、Gln含量,GAD、GABA-T、GS活力,差异均无统计学意义(P＞0.05).结论 溴苯腈中毒所致小鼠中枢神经的毒性作用可能与大脑皮层组织中GABA和Glu含量的变化有关,Na-DMPS能改善溴苯腈中毒小鼠大脑皮层组织中GABA和Glu含量.

Intervention effect of dimercaptopropansulfonate sodium on central toxic induced by bromoxynil in vivo

Objective To investigate the changes of γ-aminobutyric acid (GABA) and glutamate (Glu) in the cerebral cortex following acute bromoxynil intoxication in mice and the protective effect of sodium dimercaptopropane sulfonate (Na-DMPS). Methods 30 ICR mice were randomly divided into blank control group (10), exposure group (10) and Na-DMPS protection group (10). The levels of GABA and Glu in the cerebral cortex were measured by RP-HPLC. The glutamine (Gln) level and the glutamine synthetase (GS),glutamate decarboxylation enzyme (GAD), γ-aminobutyric acid transaminase (GABA-T) activity in the cerebral cortex were determined by U V colorimetric. Results Compared with the control group GABA: (3.41 ±0. 12)μmol/g, Glu(14.00±0.16) μmol/g, Gln(1.25±0.19) μmol/g, GAD(13.50±0.25) μmol·g-1·h-1, GABA-T(25.51±0.21)μmol·g-1·h-1, GS( 142.19±1.31 ) U/mg pro], the level of GABA(3.14±0. 14) μmol/g] was decreased (P＜0.05), whereas the level of Glu (17.54±0.40) μmol/g] and Gln (3.35±0.27) μmol/g] were increased (P＜0.05), the activity of GAD ( 11.93±0.15 ) μmol· g-1· h-1], GA BA-T(24.15±0.22) μmol · g-1· h-1],GS ( 140.75±1.01 )U/mg pro] was decreased (P＜0.05) in acute intoxication group; Compared with the acute intoxication group, the level of GABA (3.52±0.30) μmol/g] was increased (P＜0.05), whereas the level of Glu ( 14.20±0.32 ) μmol/g] and Gln ( 1.32±0.17 ) μmol/g] were decreased (P＜0.05), the activity of GAD ( 13.01 ±0.45 μmol ·g-1·h-1], GABA-T (25.19±0.26) μmol·g-1 ·h-1, GS (142.35±1.20) U/mg pro] was increased (P＜0.05 ) ;In contrast, the levels of GABA, Glu, Gln and the activity of GAD, GABA-T, and GS in Na-DMPS protection group were not significantly different in comparison with control group (P＞0.05). Conclusion The central toxic effects of mice with acute bromoxynil intoxication may be related to the changes of GABA and Glu content in the cerebral cortex;Na-DMPS can protect mice from bromoxynil-induced central toxic effects and GABA and Glu abnormal change in the cerebral cortex.