摘要
目的:探讨大鼠DRG神经元GABA激活电流的离子机制。
方法:应用全细胞膜片钳记录技术,观察钙激活氯通道阻断剂尼氟灭酸及容积调控氯通道阻断剂NPPB对大鼠急性分离DRG神经元GABA激活电流的影响。
结果: (1)尼氟灭酸可浓度依赖性地抑制GABA激活电流,IC50为27.19±4.87μmol/L,抑制率为63.9 % (n = 12);NPPB对GABA激活电流的抑制率为29.7 % (n = 9);尼氟灭酸与NPPB混合对GABA激活电流的抑制率为79.2 % (n = 6)。(2)去除细胞外液及电极内液中Ca~(2+),GABA激活电流幅值明显降低,抑制率为47.4 %(n = 6);预灌流尼群地平阻断Ca~(2+)内流,对GABA激活电流幅值的抑制达49.6% (n = 4)。
结论:钙激活氯通道及容积调控氯通道可能参与了GABAA受体激活导致Cl-外流。细胞外Ca~(2+)可经由电压依赖性钙通道内流,激活钙激活氯通道,参与GABA激活电流的形成。
二、尼氟灭酸对福尔马林致痛大鼠的行为学影响
目的:观察尼氟灭酸是否有镇痛作用,探讨其在初级感觉信息传递过程中的作用。
方法:将24只SD大鼠随机分为3组,F组:大鼠足底部注射福尔马林;NS组:大鼠足底部注射生理盐水;NFA组:大鼠腹腔注射尼氟灭酸后足底部注射福尔马林。以每5 min为一单元,记录足底部注射后每5 min大鼠注射侧缩腿次数及舔足时间以及每一单元内大鼠缩腿及咬/舔注射侧后爪的累积时间,持续60 min。
结果:(1)除静止相外,其余时间段F组及NFA组的缩腿次数与NS组相比均显著增多(p < 0.05),F组第一相0 ~ 5 min及第二相15 ~ 20 min、20 ~ 25 min、30 ~ 35 min、35 ~ 40 min舔爪时间长于NS组(p < 0.05),NFA组第一相0 ~ 5 min及第二相15 ~ 20 min、20 ~ 25 min、30 ~ 35 min的舔爪时间也长于NS组(p < 0.05)。(2) NFA与F组相比第一相的缩腿次数较多(p < 0.05),舔爪时间较长(p < 0.05),第二相缩腿次数20 ~ 25 min、30 ~ 35 min、35 ~ 40 min、40 ~ 45 min少于F组(p < 0.05),第二相舔爪时间20 ~ 25 min、25 ~30 min、30 ~ 35 min、35 ~ 40 min短于F组(p < 0.05)。(3) NFA组第一相缩腿及咬/舔注射侧后爪的累积时间较F组长,而第二相缩腿及咬/舔注射侧后爪的累积时间较F组短。
结论:尼氟灭酸在福尔马林致痛大鼠模型第一相急性痛期起到致痛作用;尼氟灭酸在福尔马林致痛大鼠模型第二相持续反应期起到镇痛作用。
Part 1. The effects of chloride channel blockers on GABA-activated current of isolated adult rat dorsal root ganglion neurons
Objective: To investigate the effect of calcium-activated chloride channels (CaCC) blocker niflum -ic acid and volume-regulated chloride channels (VRCC) blocker NPPB on GABA- activated curr ent (IGABA).
Methods: The effect of CaCC blocker niflumic acid and VRCH blocker NPPB on GABA-activat- ed current was examined in acutely dissociated neurons of rat dorsal root ganglia by using whole- cell patch clamp methods.
Conclusion: It was suggested that CaCC and VRCH may be involved in the IGABA in rat DRG ne- urons. The increase of intracellular Ca~(2+) concentration caused by influx of extracellular Ca~(2+) may be able to activate CaCC and modulate the IGABA .
Part 2. The effects of niflumic acid on rat’s behavior response in formalin test.
Objective: To investigate the analgesic effect of niflumic acid in rat formalin induced inflammato- ry pain .
Methods: 24 SD rats were randomly divided into 3 groups, Group NS: normal saline group; Gro- up F: formalin group; Group NFA: Niflumic acid group. Investigate and record the fliching , bitin- gand liching time after 5min, 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min.
Results:(1) Compare the F group and the NFA group with the NS group,fliching , biting/liching ti- me obviously increased (P<0.05),except 5min ~10 min showed no diff-erence (P>0.05), fliching , biting/liching time obviously increased (P<0.05). (2) Compare NFA group with F group, the flich- ing and biting/liching time obviously increased in the first phase (p < 0.05), the fliching and biting /liching time obviously decreased obviously in the second phase 20~25 min、25 ~30 min、30 ~ 35 min、35 ~ 40 min (P<0.05).
Conclusion: According to the experimental results, effects of niflumic acid increase pain in the f- irst phase of formalin test by inhibiting the presynaptic inhibition and release pain in the second p- hase of formalin test by inhibiting the synthesis of PGs.
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