Department of Anesthesiology and Pain Clinic, The Affiliated Lianyungang Oriental Hospital of Bengbu Medical College, Lianyungang, Jiangsu, China.
Department of Critical Care Medicine, The Affiliated Lianyungang Oriental Hospital of Bengbu Medical College, Lianyungang, Jiangsu, China.
Synapse. 2021 Oct;75(10):e22219. doi: 10.1002/syn.22219. Epub 2021 Jul 30.
Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol (Pro) and their paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured. In addition, the expression patterns of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10 were detected. CCI rats treated with propofol were further injected with antagomiR-140-3p to verify the role of miR-140-3p in propofol's analgesic actions. In addition to confirming the relationship between miR-140-3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol-treated CCI rats were also injected with Ad-JAG1 (adenovirus-packaged JAG1 overexpression vector and Ad-NC) to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway-related proteins were detected RESULTS: Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up-regulating the expression of IL-10 and inhibiting the release of TNF-α and IL-1β. Mechanically, propofol enhanced the amount of miR-140-3p in CCI rats via the regulation of JAG1. Down-regulation of miR-140-3p, or up-regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR-140-3p/JAG1 to realize its analgesic effect CONCLUSION: Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP.
慢性坐骨神经缩窄损伤（CCI）被用于建立大鼠神经病理性疼痛（NP）模型。然后，用丙泊酚（Pro）处理 CCI 大鼠，并测量其足底撤回机械阈值（PWMT）和足底撤回热潜伏期（PWTL）。此外，还检测了肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和 IL-10 的表达模式。用丙泊酚处理的 CCI 大鼠进一步注射抗 miR-140-3p，以验证 miR-140-3p 在丙泊酚镇痛作用中的作用。除了确认 miR-140-3p 与 JAG1 之间的关系外，还检测了 JAG1 本身的表达模式。用丙泊酚处理的 CCI 大鼠还注射了 Ad-JAG1（腺病毒包装的 JAG1 过表达载体和 Ad-NC），以测试 JAG1 在丙泊酚镇痛作用机制中的作用。最后，检测了 JAG1 和 Notch 通路相关蛋白的水平。结果：发现丙泊酚可缓解 NP，包括热痛觉过敏和机械痛觉阈值。丙泊酚还可以通过上调 IL-10 的表达和抑制 TNF-α和 IL-1β的释放来改善神经炎症。从机制上讲，丙泊酚通过调节 JAG1 增加了 CCI 大鼠中 miR-140-3p 的含量。下调 miR-140-3p 或上调 JAG1 可降低丙泊酚对 NP 的保护作用。丙泊酚通过 miR-140-3p/JAG1 抑制 Notch 信号通路的激活来实现其镇痛作用。结论：我们的研究结果表明，丙泊酚通过 miR-140-3p/JAG1 抑制炎症反应和 Notch 信号通路来缓解 NP。这些数据为 NP 的潜在临床治疗提供了证据支持。
