TLR4/NF-κB信号通路在切口痛作用机制中的实验研究

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Abstract Objective To investigate the mechanism of Toll like receptor 4 (TLR4)/ nuclear factor κB (NF-κB) signal pathway in rats with incisional pain. Methods One hundred healthy adult male Sprague-Dawley (SD) SPF rats of 20 weeks old were selected to establish incision pain models. Before operation and after operation for 0.5 h, 1 h, 2 h, 8 h, 12 h, 1 d, 2 d, 3 d, 5 d, 7 d, the mechanism withdraw threshold (MWT) in non-operative side and operative side of rats were detected by electronic von Frey pressure pain threshold detector. Before operation and after operation for 2 h, 8 h, 1 d, 2 d, 3 d, 5 d and 7 d, the expression of TLR4, NF-κB, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the spinal cord were detected by real-time fluorescence quantitative PCR (real-time PCR). Results After operation, the MWT in the operative side of rats was lower than that before operation, which was the lowest after operation for 2 h, then increased gradually, and they were significantly lower than those of non-operative side (P ＜ 0.05). After operation, the expression levels of TLR4, NF-κB, IL-1β and TNF-α in spinal cord of rats were increased compared with those before operation, which of postoperative 2 h, 8 h, 1 d, 2 d and 3 d had statistically significant differences compared with those before operation (P ＜ 0.05), which of postoperative 5 d and 7 d had no statistically significant differences compared with those before operation (P ＞ 0.05). The expression levels of TLR4 and NF-κB in the spinal cord reached the highest after operation for 1 d, and the expression levels of IL-1β and TNF-α reached the highest after operation for 8 h. Pearson correlation analysis showed that there was a negative correlation of MWT in operative side with the expression of TLR4 and NF-κB (r = -0.473, P ＜ 0.05, r = -0.398； P ＜ 0.05), the TLR4 levels in spinal cord of rats were positively correlated with the expression levels of IL-1β and TNF-α (r = 0.302, P ＜ 0.05; r = 0.538, P ＜ 0.05), and the NF-κB levels in spinal cord of rats were positively correlated with the expression levels of IL-1β and TNF-α (r = 0.283, P ＜ 0.05; r = 0.467, P ＜ 0.05). Conclusion The signal pathway of TLR4/NF-κB in spinal cord of rats with incisional pain is activated, the expression levels of TLR4 and NF-κB are increased, and the expression levels of downstream inflammatory cytokines IL-1β and TNF-α are up-regulated, which is involved in the regulation process of incisional pain.

Key words： Toll like receptor 4 Nuclear factor κB Incisional pain Rat

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	LIU Dehua1 WANG Jian2 GAO Zhiqiang1 ZOU Liansheng1 XU Ying3

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LIU Dehua1 WANG Jian2 GAO Zhiqiang1 ZOU Liansheng1 XU Ying3. Experimental study of TLR4/NF-κB signal pathway in the mechanism of incisional pain[J]. 中国医药导报, 2018, 15(4): 23-26.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2018/V15/I4/23

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