高压氧对神经病理性疼痛大鼠p38 MAPK信号通路的影响

Effect of Hyperbaric Oxygen on p38 MAPK Signal Transduction Pathway in Neuropathic Rats

目的探讨高压氧对神经病理性疼痛大鼠p38 MAPK信号通路的影响,从而明确其作用机制。方法实验分为2部分,每部分选用30只SD大鼠,又随机分为3组:假手术组(S组)、坐骨神经慢性缩窄组(CCI组)和高压氧组(HBO组),每组10只。第一部分实验测定术后3,7,14,28 d疼痛行为学指标,并在术后28 d取脊髓标本Western blot方法检测磷酸化p38表达,免疫组化法检测P2X4受体;第二部分实验先对各组大鼠行腰段鞘内置管,并将p38 MAPK信号通路阻断剂(SB203580)连续注入蛛网膜下腔中,测定阻断p38 MAPK信号通路后3,7,14,28 d疼痛行为学指标及术后28 d免疫组化法检测P2X4受体。结果第一部分实验中CCI组、HBO组大鼠疼痛行为学评分较S组明显降低(P<0.05),且CCI组比HBO组降低显著(P<0.05)。CCI组、HBO组的磷酸化p38及P2X4受体含量较S组增加(P<0.05),且CCI组磷酸化p38及P2X4受体的表达比HBO组显著增加(P<0.05)。第二部分实验中大鼠p38 MAPK信号通路抑制后,CCI组、HBO组疼痛行为学评分无统计学差异(P>0.05),但与未给抑制剂第一部分实验的CCI组、HBO组比较明显增高(P<0.05);CCI组及HBO组的P2X4受体表达比S组显著增高(P<0.05),但2组间比较无统计学差异(P>0.05)。结论高压氧可能通过P2X4受体介导的p38 MAPK信号通路影响神经病理性疼痛大鼠。

Objective To investigate the effect of hyperbaric oxygen（HBO）on p38 MAPK signal pathway in neuropathic pain,and explore its mechanism. Methods The experiment was divided into two parts with thirty SD rats in each part. Each part was then randomly divided into 3groups：sham operation group（S group）,chronic constriction group（CCI group）and hyperbaric oxygen group（HBO group）,with 10 rats in each group. Part one：Pain-related behavior were detected on 3 day,7 day,14 day,28 day after operation. Phosphorylative p38 was detected by Western blot method and the P2X4 receptor was detected by immunohistochemistry method on the 28 th day. Part two：All the rats were treated with SB203580. Pain-related behavior were detected on 3 day,7 day,14 day,28 day after operation. P2X4 receptor was detected by immunohistochemistry method on the 28 th day. Results CCI and HBO groups were significantly lower than S group in pain-related behaviors（P〈0.05）. CCI group was significantly lower than that in HBO group（P〈0.05）. The content of phosphorylative p38 and P2X4 receptor in CCI and HBO group were increased（P〈0.05）,and the expression of phosphorylative p38 and P2X4 in CCI group was significantly increased than that in HBO group（P〈0.05）. When p38 MAPK was inhibited,pain-related behavior in HBO and CCI group increased significantly than the pain-related behavior of HBO and CCI group in Part 1（P〈0.05）. But the difference between group CCI and HBO was not significant（P〉0.05）. Though the expression of P2X4 receptor in CCI group and HBO group was significantly higher than that in S group（P〈0.05）,the difference between group CCI and HBO was not significant（P〉0.05）. Conclusion Hyperbaric oxygen therapy can affect the expression of p38 MAPK through P2X4 receptor in rats of neuropathic pain.