Jiang Yinghai, Wang Jing, Li Haiqin, Xia Lingjie
Pain Department, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003 Henan China.
J Inflamm (Lond). 2019 Jul 23;16:19. doi: 10.1186/s12950-019-0217-z. eCollection 2019.
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.
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.
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.
IL-35 treatment mitigated DNP via downregulating JNK signaling pathway.
新出现的证据表明，炎症参与了糖尿病性神经病理性疼痛（DNP）的发生和发展。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。本研究旨在探讨IL-35是否能减轻链脲佐菌素（STZ）诱导的大鼠模型中的DNP及其潜在机制。
通过单次注射STZ建立DNP大鼠模型，随后测量空腹血糖和胰岛素。STZ注射14天后，分别向DNP大鼠鞘内注射IL-35、c-Jun氨基末端激酶（JNK）抑制剂或激活剂或二甲基亚砜（DMSO）作为溶剂对照。测定机械性异常性疼痛以评估IL-35的治疗效果。在机制研究中，使用酶联免疫吸附测定（ELISA）和蛋白质印迹法进一步评估炎症细胞因子的血清和蛋白质水平，并通过定量逆转录聚合酶链反应（qRT-PCR）评估JNK信号的激活。通过尼氏染色评估组织病理学变化。使用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色检测细胞凋亡。
DNP大鼠表现出空腹血糖和胰岛素水平升高以及胰岛素敏感性指数（ISI）降低。鞘内注射IL-35减少了DNP大鼠脊髓中促炎细胞因子的积累。此外，IL-35通过抑制JNK途径发挥抗炎和抗凋亡作用。
IL-35治疗通过下调JNK信号通路减轻了DNP。
