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目的:探讨N-甲基-D-天冬氨酸(NMDA)受体阻滞剂地卓西平(MK-801)拮抗水杨酸钠(SS)对豚鼠耳毒性的实验研究。方法:将48只成年豚鼠随机分成4组,每组12只:A组为空白对照组;B组为水杨酸钠组,腹腔注射水杨酸钠;C组为水杨酸钠与人工外淋巴液(APL)组,APL滴于明胶海绵置于左耳圆窗龛,同时腹腔注射水杨酸钠;D组为水杨酸钠与MK-801组,MK-801滴于明胶海绵置于左耳圆窗龛,同时腹腔注射水杨酸钠。给药10天后,免疫组织化学染色法检测4组豚鼠耳蜗螺旋神经节(SGN)内凋亡调控因子caspase-3蛋白表达情况,TUNEL法检测细胞凋亡情况。结果:A组SGN内caspase-3表达量少,B、C2组表达量明显高于A组(p<0.01),而D组与B、C相比,caspase-3表达量较低(p<0.01),但仍高于A组(P<0.01)。TUNEL检测结果显示B、C、D3组SGN凋亡率均明显高于A组(p<0.01),而D组SGN凋亡率低于B、C2组(P<0.01)。结论:腹腔持续注射大量水杨酸钠可引起豚鼠螺旋神经节细胞caspase-3表达量和细胞凋亡率增高;MK-801经耳蜗圆窗龛局部给药可在一定程度上拮抗水杨酸钠引起的的耳毒性。
AIM: To investigate the antagonism of sodium salicylate (SS) by diltiazem (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, on guinea pig ototoxicity. Methods: 48 adult guinea pigs were randomly divided into 4 groups of 12 rats in each group: group A was blank control group; group B was sodium salicylate group, intraperitoneal injection of sodium salicylate; group C was sodium salicylate and artificial In the APL group, APL was dropped into gelatin sponge in the left ear round window niche with intraperitoneal injection of sodium salicylate; group D was sodium salicylate and MK-801 group, and MK-801 was dropped on gelatin sponge Left ear round window niche, while intraperitoneal injection of sodium salicylate. Ten days after the administration, the expression of caspase-3 protein in the spiral ganglion (SGN) of four groups of guinea pigs was detected by immunohistochemistry and the apoptosis was detected by TUNEL method. Results: The expression of caspase-3 in group A was lower than that in group A and B (P <0.01), while the expression of caspase-3 in group B was lower than that of group B and C (p < 0.01), but still higher than the A group (P <0.01). The results of TUNEL showed that the apoptotic rates of SGN in groups B, C and D3 were significantly higher than those in group A (P <0.01), while the apoptosis rate of SGN in group D was lower than that of groups B and C2 (P <0.01). CONCLUSION: Sustained intraperitoneal injection of large amount of sodium salicylate causes caspase-3 expression and apoptosis in guinea-pig spiral ganglion cells. Local administration of MK-801 through the cochlea round-window niche may antagonize the effect of sodium salicylate Caused ototoxicity.