Nrf2/HO-1通路在腹腔注射红景天苷缓解小鼠骨癌痛中的作用 *

The role of Nrf2/HO-1 pathway in the relief of bone cancer pain in mice by intraperitoneal injection of salidroside *

摘要:

目的：明确Nrf2/HO-1通路在腹腔注射红景天苷 (salidroside, Sal) 缓解小鼠骨癌痛 (bone cancer pain, BCP) 中的作用。 方法：第一部分,雄性C57BL/6小鼠28只,随机数字表法分为两组,假手术组(Sham 组,n = 8)和BCP组 (n = 20)；第二部分,雄性C57BL/6小鼠48只,随机数字表法分为四组,Sham组 (n = 12)、BCP组 (n = 12)、Sal组 (n = 12) 和Sal + 葫芦巴碱 (trigonelline, Trig) 组 (n = 12)。von Frey和热辐射刺激仪分别测定小鼠机械刺激缩足阈值 (menchanical withdrawal threshold, MWT) 和热刺激缩足反射潜伏期 (thermal withdrawal latency, TWL)；HE染色观察股骨；Western Blot和免疫荧光检测脊髓Nrf2和HO-1表达。 结果：造模后7天,BCP组MWT和TWL降低并持续至造模后21天 (P < 0.001)；Western Blot和免疫荧光结果显示,BCP组脊髓中Nrf2 (P < 0.01) 和HO-1 (P < 0.001) 在造模后7天表达上调,而在造模后14天 (P < 0.05) 和21天下调；与BCP组相比,腹腔注射Sal提高小鼠MWT和TWL (P < 0.001),且上调脊髓中Nrf2和HO-1表达 (P < 0.05),这种作用被Trig阻断。 结论：腹腔注射Sal可能通过活化Nrf2/HO-1通路缓解小鼠BCP。

Abstract:

Objective: To determine the role of nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) pathway in the relief of mice with bone cancer pain (BCP) by intraperitoneal injection of salidroside (Sal). Methods: In the first part, twenty-eight male C57BL/6 mice were randomly divided into two groups: Sham group (n = 8) and BCP group (n = 20); In the second part, forty-eight male C57BL/6 mice were randomly divided into four groups: Sham group (n = 12), BCP group (n = 12), Sal group (n = 12) and Sal + Trigonelline (Trig) group (n = 12). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed with von Frey filaments and thermal radiation stimulator; The femur were observed by hematoxylin-eosin staining; Western BlotSand immunofluorescence were used to detect the expressions of Nrf2 and HO-1 in the spinal cord. Results: On the 7 days after modeling, the MWT and TWL of BCP group decreased and continued to decrease to 21 days after modeling (P < 0.001). The results of Western Blot and immunofluorescence showed that the expression of Nrf2 (P < 0.01) and HO-1 (P < 0.001) in spinal cord of BCP group increased on the 7 days after modeling, However, it decreased on the 14 days (P < 0.05) and 21 days after modeling. Compared with BCP group, the intraperitoneal injection of Sal increased MWT and TWL (P < 0.001), and increased the expression of Nrf2 and HO-1 in spinal cord (P < 0.05). This effect was blocked by Trig. Conclusion: Intraperitoneal injection of Sal may alleviate BCP in mice by activating Nrf2/HO-1 pathway.