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| 钙库调控钙离子通道在瑞芬太尼诱发切口痛觉过敏中的作用 |
| Effect of store-operated calcium channel on remifentanil-induced postoperative hyperalgesia in rats |
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| DOI：10.12089/jca.2021.04.016 |
| 中文关键词: 瑞芬太尼 痛觉过敏 钙库调控钙离子通道 钙离子/钙调素依赖的蛋白激酶Ⅱα |
| 英文关键词: Remifentanil Hyperalgesia Store-operated calcium channels Ca2+/calmodulin-dependent protein kinasesⅡα |
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| 中文摘要: |
目的 探讨钙库调控钙离子通道（SOCC）在瑞芬太尼诱发的切口痛觉过敏中的作用。
方法 雄性SD大鼠36只，2～3个月龄，体重360～380 g，采用随机数字表法分为四组：对照组（C组，n=8）、切口痛组（I组，n=9）、切口痛+瑞芬太尼组（IR组，n=9）、切口痛+瑞芬太尼+SOCC抑制剂（YM-58483）组（Y组，n=10）。IR组和Y组尾静脉泵注瑞芬太尼1 μg·kg-1·min-1，持续60 min；C组和I组尾静脉泵注生理盐水0.1 ml·kg-1·min-1，持续60 min。I组、IR组和Y组于给药后10 min于右后足底做一切口，于给药前24 h（T0）、给药后2 h（T1）、6 h（T2）、24 h（T3）、48 h（T4）测定大鼠热缩足潜伏期（TWL）和机械缩足阈值（MWT）。Y组于每次行为学测试前2 h鞘内注射10 μl浓度为1000 μmol/L的SOCC抑制剂YM-58483，其余各组注射等容量溶剂PEG300。取L4-6节段脊髓，采用免疫荧光组织化学法检测脊髓背角SOCC主要蛋白基质相互作用分子1（STIM1）和Orai1阳性细胞计数，采用Western blot法检测脊髓背角STIM1和Orai1以及磷酸化的钙离子/钙调素依赖的蛋白激酶Ⅱα（p-CaMKⅡα，CaMKⅡα的激活状态）蛋白含量。
结果 与C组比较，T1—T4时IR组TWL明显缩短、MWT明显降低（P＜0.05），I组、IR组和Y组脊髓背角STIM1和Orai1阳性信号细胞数、STIM1和Orai1蛋白含量、脊髓p-CaMKⅡα蛋白含量明显增加（P＜0.05）。与I组比较，IR组和Y组脊髓背角STIM1和Orai1阳性信号细胞数、STIM1和Orai1蛋白含量、IR组脊髓p-CaMKⅡα蛋白含量明显增加（P＜0.05）。与IR组比较，Y组T1—T4时TWL明显延长（P＜0.05），T2—T4时MWT明显升高（P＜0.05），Y组脊髓p-CaMKⅡα蛋白含量明显减少（P＜0.05）。
结论 SOCC蛋白含量增加参与了瑞芬太尼诱发切口痛觉过敏的形成，鞘内注射SOCC抑制剂YM-58483明显减少了p-CaMKⅡα蛋白含量，改善了大鼠由瑞芬太尼诱发的切口痛觉过敏，提示脊髓中SOCC通路通过磷酸化CaMKⅡα参与了瑞芬太尼诱发切口痛觉过敏的形成。 |
| 英文摘要: |
Objective To investigate the effect of store-operated calcium channel on remifentanil-induced postoperative hyperalgesia in rats.
Methods Thirty-six adult male SD rats of two to three-month-old, weighing 360-380 g were randomly divided into four groups: control group (group C, n = 8),incision pain group (group Ⅰ, n = 9), incision pain + remifentanil group (group IR, n = 9) and incision pain + remifentanil + SOCC inhibitor (YM-58483) group (group Y, n = 10). In groups IR and Y, remifentanil was infused intravenously 1 μg ·kg-1·min-1 for 60 minutes. In groups C and I, normal saline was infused intravenously 0.1 ml·kg-1·min-1 for 60 minutes. In groups I, IR and Y, 1 cm longitudinal incision was made in the plantar surface of the right hind paw. Paw withdrawal thermal latency (TWL)and mechanical withdrawal threshold (MWT) were measured at 24 hours before dosing(T0) and 2 hours (T1), 6 hours (T2), 24 hours (T3), and 48 hours (T4) after remifentanil or normal saline administration. YM-58483 was dissolved in PEG300 for intrathecal injection at the concentration of 1 000 μmol/L (10 μl) and applied at 2 hours before each behavior test in group Y. The same volume of PEG300 was used as control treatment. After the test, four groups of rats were sacrificed and L4-6 spinal cord tissues were sampled. Then, western blot was performed to examine the expression of spinal STIM1, Orai1 and p-CaMKⅡα (the activation state of CaMKⅡα). Immunofluorescence was used to detect the positive cells of STIM1 and Orai1 in the spinal dorsal horn.
Results Compared with group C, TWL was significantly shortened and MWT was significantly decreased at T1-T4 in group IR (P < 0.05); the expression of spinal STIM1 and Orai1,the protein content of p-CaMKⅡα were up-regulated in groups I, IR and Y.Compared with group I,the expression of spinal STIM1 and Orai1were significantly increased in groups IR and Y (P < 0.05); the protein content of p-CaMKⅡα were significantly increased in group IR (P < 0.05). Compared with group IR, TWL was significantly lengthened at T1-T4, MWT was significantly increased at T2-T4, the protein content of p-CaMKⅡα was significantly decreased in group Y (P < 0.05).
Conclusion Intrathecal injection of YM-58483 significantly decreases the expression of p-CaMKⅡα and inhibits remifentanil-induced postoperative hyperalgesia in rats,suggesting that SOCC is involved in the development and progression of remifentanil-induced postoperative hyperalgesia via phosphorylation of CaMKⅡα. |
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