Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Toxicol Appl Pharmacol. 2021 Apr 1;416:115468. doi: 10.1016/j.taap.2021.115468. Epub 2021 Feb 25.
High glucose (HG)-induced nucleotide-binding and oligomerization (NACHT) domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome activation leads to diabetic neuropathic pain. We recently showed that salidroside could suppress NLRP3 inflammasome activation in hepatocytes exposed to HG. The aim of this study was to evaluate the analgesic effect of salidroside on diabetic rats and to explore its underlying mechanisms. Rat models with diabetic neuropathic pain were induced by high-fat diet feeding combined with low dose streptozotocin injections. Doses of salidroside at 50 and 100 mg.kg.day were administered by gavage to diabetic rats for 6 weeks. Mechanical allodynia test, thermal hyperalgesia test and biochemical analysis were performed to evaluate therapeutic effects. Primary dorsal root ganglion (DRG) cells exposed to HG at 45 mM were used to further study the effects of salidroside on the AMP-activated protein kinase (AMPK)-NLRP3 inflammasome axis and insulin sensitivity in vitro. Salidroside administration improved hyperglycemia, ameliorated insulin resistance, and alleviated neuropathic pain in diabetic rats. Moreover, salidroside induced AMPK activation and suppressed NLRP3 inflammasome activation in the DRGs of diabetic rats. In addition, salidroside treatment relieved oxidative stress, improved insulin sensitivity and regulated the AMPK-NLRP3 inflammasome axis in HG-treated DRGs in vitro. Furthermore, AMPK inhibition in vivo or AMPK silencing in vitro abolished the beneficial effects of salidroside on diabetic neuropathic pain. Together, these results indicate that salidroside alleviates diabetic neuropathic pain through its regulation of the AMPK-NLRP3 inflammasome axis in DRGs.
高糖（HG）诱导的核苷酸结合寡聚化（NACHT）域、富含亮氨酸重复（LRR）和吡喃结构域（PYD）的含 N 端蛋白 3（NLRP3）炎性小体激活导致糖尿病性神经病理性疼痛。我们最近表明，红景天苷可抑制暴露于 HG 的肝细胞中 NLRP3 炎性小体的激活。本研究旨在评估红景天苷对糖尿病大鼠的镇痛作用，并探讨其潜在机制。通过高脂肪饮食喂养结合小剂量链脲佐菌素注射诱导糖尿病神经病理性疼痛大鼠模型。通过灌胃给予红景天苷 50 和 100 mg.kg.day 的剂量，对糖尿病大鼠进行 6 周治疗。进行机械性痛觉过敏试验、热超敏反应试验和生化分析以评估治疗效果。体外将原代背根神经节（DRG）细胞暴露于 45 mM HG 进一步研究红景天苷对 AMP 激活蛋白激酶（AMPK）-NLRP3 炎性小体轴和胰岛素敏感性的影响。红景天苷给药改善了高血糖症，改善了胰岛素抵抗，并缓解了糖尿病大鼠的神经病理性疼痛。此外，红景天苷诱导 AMPK 激活并抑制糖尿病大鼠 DRG 中 NLRP3 炎性小体的激活。此外，红景天苷治疗减轻了 HG 处理的 DRG 中的氧化应激，改善了胰岛素敏感性，并调节了 AMPK-NLRP3 炎性小体轴。此外，体内 AMPK 抑制或体外 AMPK 沉默消除了红景天苷对糖尿病性神经病理性疼痛的有益作用。总之，这些结果表明红景天苷通过调节 DRG 中的 AMPK-NLRP3 炎性小体轴缓解糖尿病性神经病理性疼痛。
