摘要
【目的】观察G蛋白门控内向整流钾离子通道亚单位2(GIRK2)在瑞芬太尼诱导的痛觉过敏大鼠背根神经节和脊髓背角中的表达和分布的变化。【方法】成年雄性SD大鼠尾静脉输注瑞芬太尼4μg/(kg·min)2 h建立痛觉过敏模型。瑞芬太尼注射后6 h、1 d、3 d和5 d,采用免疫荧光化学法观察GIRK2在瑞芬太尼诱导痛觉过敏大鼠的背根神经节(DRG)和脊髓背角中分布的变化。采用免疫印迹法检测大鼠背根神经节和脊髓背角GIRK2总蛋白和膜蛋白的表达。最后,采用行为学评价瑞芬太尼输注后,鞘内注射GIRK2特异性激动剂ML297对痛阈的影响。【结果】免疫荧光结果显示,在背根神经节和脊髓背角I-II板层,GIRK2主要与IB4阳性的小神经元及其神经纤维共定位,而瑞芬太尼注射后GIRK2表达显著降低。免疫印迹结果显示,静脉输注瑞芬太尼1 d后,与对照组相比,背根神经节GIRK2总蛋白(0.47±0.10 vs.1.01±0.17,P<0.001)和膜蛋白(0.47±0.11 vs.1.06±0.12,P<0.001)表达水平均显著减少;与背根神经节结果相一致的是,脊髓背角GIRK2总蛋白水平(0.52±0.09 vs.1.10±0.08,P<0.001)和膜蛋白表达水平(0.54±0.10 vs.1.01±0.13,P<0.001)也显著降低。行为学结果显示,与生理盐水组相比,在瑞芬太尼处理大鼠,ML297延长热撤足潜伏期的作用显著降低(P<0.001)。【结论】持续静脉输注瑞芬太尼可能通过诱导大鼠背根神经节和脊髓背角GIRK2表达下调诱发痛觉过敏。
【Objective】To observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2(GIRK2)in the dorsal root ganglion(DRG)and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia.【Methods】Hyperalgesia was induced by intravenous infusion of remifentanil 4μg/kg/min for 2 h in adult male SD rats.At 6th hour and on days 1,3 and 5 following remifentanil treatment,we used immunofluorescence to examine the changes in the GIRK2 distribution and expression.Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats.Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion.【Results】mmunofluorescence results showed that GIRK 2 was mainly co-localized with IB 4-positive small neurons in DRG and nerve fibers in spinal dorsal horn.GIRK 2 expression was significantly downregulated following remifentanil treatment.Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil,com-pared with those in the control group,GIRK 2 expression levels of the total protein and membrane protein in DRG(0.47±0.10 vs.1.01±0.17,P<0.001;0.47±0.11 vs.1.06±0.12,P<0.001)and spinal dorsal horn(0.52±0.09 vs.1.10±0.08,P<0.001;0.54±0.10 vs.1.01±0.13,P<0.001)were all significantly decreased.The behavioral results showed that intrathecal ML 297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment(P<0.001).【Conclusions】Remifentanil might induce hyperalgesia via down-regulating GIRK 2 expression in rat DRG and spi-nal cord dorsal horn.
作者
罗国娅
王晓娥
李林芝
王文慧
杨翘睿
陈元
肖力
崔宇
LUO Guo-ya;WANG Xiao-e;LI Lin-zhi;WANG Wen-hui;YANG Qiao-rui;CHEN Yuan;XIAO Li;CUI Yu(SunYat-sen University School of Medicine,Shenzhen 518107,China;Department of Anesthesiology,The First Affiliated Hospital,SunYat-sen University,Guangzhou 510080,China)
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2023年第3期361-368,共8页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金(82101344)
广东省自然科学基金(2021A1515010588)。
