Background Emerging evidence has demonstrated that inflammation is involved in the occurrence and development of diabetic neuropathic pain (DNP). The anti-inflammatory property of interleukin (IL)-35 makes it a promising candidate to block the pain perception. The present study was undertaken to investigate whether IL-35 could attenuate DNP in streptozotocin (STZ)-induced rat model and its potential mechanism. Methods The rat model of DNP was established by a single STZ injection followed by measurements of fasting blood glucose and insulin. Fourteen days after STZ injection, DNP rats were intrathecally injected with IL-35, c-Jun N-terminal kinase (JNK) inhibitor or activator or dimethylsulfoxide (DMSO) as vehicle control, respectively. The mechanical allodynia was assayed to evaluate the therapeutic effect of IL-35. In mechanism study, the serum and protein levels of inflammatory cytokines using ELISA and western blotting and the activation of JNK signaling were further evaluated by quantitative reverse transcription PCR (qRT-PCR). Histopathologic changes were evaluated by Nissl staining. Apoptosis was examined using TUNEL staining. Results DNP rats exhibited increased fasting blood glucose and insulin levels and reduced insulin sensitivity index (ISI). Intrathecal injection of IL-35 reduced accumulation of pro-inflammatory cytokines in the spinal cord of DNP rats. Furthermore, IL-35 displayed anti-inflammatory and anti-apoptotic effects via inhibition of JNK pathway. Conclusion IL-35 treatment mitigated DNP via downregulating JNK signaling pathway.

中文翻译：

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IL-35 通过抑制 JNK 信号传导来减轻糖尿病神经性疼痛大鼠模型中的炎症进展。

背景 新出现的证据表明，炎症与糖尿病神经性疼痛 (DNP) 的发生和发展有关。白细胞介素 (IL)-35 的抗炎特性使其成为阻断疼痛感知的有希望的候选者。本研究旨在调查IL-35是否可以减弱链脲佐菌素（STZ）诱导的大鼠模型中的DNP及其潜在机制。方法建立大鼠DNP模型，单次注射STZ，测定空腹血糖和胰岛素。STZ 注射后 14 天，DNP 大鼠分别鞘内注射 IL-35、c-Jun N-末端激酶 (JNK) 抑制剂或激活剂或二甲亚砜 (DMSO) 作为载体对照。测定机械异常性疼痛以评估IL-35的治疗效果。在机理研究中，通过定量逆转录PCR（qRT-PCR）进一步评估使用ELISA和蛋白质印迹的炎性细胞因子的血清和蛋白质水平以及JNK信号传导的激活。通过 Nissl 染色评估组织病理学变化。使用 TUNEL 染色检查细胞凋亡。结果 DNP大鼠表现出空腹血糖和胰岛素水平升高，胰​​岛素敏感性指数（ISI）降低。鞘内注射 IL-35 可减少 DNP 大鼠脊髓中促炎细胞因子的积累。此外，IL-35 通过抑制 JNK 通路表现出抗炎和抗凋亡作用。结论 IL-35 治疗通过下调 JNK 信号通路减轻 DNP。