南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (6): 937-941.doi: 10.12122/j.issn.1673-4254.2021.06.18

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獐牙菜苦苷可减轻糖尿病大鼠的周围神经痛：基于抑制NOXS/ROS/NLRP3通路实验

王 保，姚嘉茵，尧新华，劳俊铭，刘 栋，陈陈燕，鲁 义   

  • 出版日期:2021-06-20 发布日期:2021-07-05

Swertiamarin alleviates diabetic peripheral neuropathy in rats by suppressing NOXS/ROS/NLRP3 signal pathway

  • Online:2021-06-20 Published:2021-07-05

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摘要： 目的 基于NOXS/ROS/NLRP3信号通路探讨獐牙菜苦苷对糖尿病周围神经痛（DPN）大鼠的治疗作用及分子机制。方法 采用链脲佐菌素(STZ)法构建大鼠模型，造模成功后第1、7、14天分别按大鼠体质量腹腔注射干预制剂。将32只SD大鼠随机分为4组：空白对照组、DPN模型组、獐牙菜苦苷治疗组、NOXS抑制剂治疗组。空白对照组：给予10 mL/kg生理盐水；DPN模型组：给予10 mL/kg生理盐水；獐牙菜苦苷治疗组：给予5 mg/kg獐牙菜苦苷；NOXS抑制剂治疗组：给予10 mL/kg二苯基氯化碘盐。在给药完毕30 min后，对各组大鼠进行触觉过敏试验，采用ELISA检测NOXS/ROS/NLRP3以及炎性因子表达水平，采用Western blot方法检测各组大鼠脊髓组织的NOXS/ROS/NLRP3表达水平。结果 与空白对照组比较，DPN模型组大鼠在造模后出现痛觉过敏（P<0.001），促炎因子TNF-α以及IL-6表达升高（P<0.001），抑炎因子TGF-β表达下降（P<0.001），NOXS/ROS/NLRP3通路各因子表达升高（P<0.001）。獐牙菜苦苷干预后有效减轻触觉过敏（P<0.001），且抑制促炎因子TNF-α（P=0.03）以 及IL-6（P=0.002）的表达，促进抑炎因子TGF-β的表达（P=0.04）；并且下调NOXS（P<0.001）、ROS（P<0.001）以及NLRP3（P= 0.002）通路各因子的表达水平。獐牙菜苦苷对炎性因子及NOXS/ROS/NLRP3通路各因子的表达影响与NOXS抑制剂治疗组间差异无统计学意义（P>0.05）。结论 獐牙菜苦苷有效缓解触觉过敏，治疗DPN，通过抑制NOXs/ROS/NLRP3信号通路表达，纠正DPN炎性因子失衡是其分子机制之一。

关键词: 獐牙菜苦苷；糖尿病周围神经痛；NLRP3；炎性平衡

Abstract: Objective To observe the therapeutic effect of swertiamarin on diabetic peripheral neuropathy (DPN) in rats and explore the molecular mechanism in light of the NOXS/ROS/NLRP3 signal pathway. Methods Thirty-two SD rats were randomly divided into control group, DPN model group (treated with saline), swertiamarin (5 mg/kg) treatment group and NOXS inhibitor (10 mL/kg DPI) treatment group. Rat models of DPN were established in the latter 3 groups by intraperitoneal injections of STZ, and the treatments were administered on days 1, 7 and 14 after modeling. Tactile hypersensitivity of the rats was evaluated 30 min after the treatment. The expressions of NOXS, ROS, NLRP3 and inflammatory factors in the spinal cord tissue were detected using ELISA, and the protein expressions of NOXS, ROS, and NLRP3 were also detected with Western blotting. Results Compared with those in the control group, the rats in DPN group showed significant hyperalgesia (P<0.001), increased expressions of TNF-α (P<0.001) and IL-6 (P<0.001), decreased expressions of TGF-β (P<0.001), and increased expressions of NOXS/ROS/NLRP3 signal pathway (P<0.001). Compared with those in DPN model group, the rats with swertiamarin treatment showed improved hyperalgesia (P<0.001), decreased expressions of TNF-α (P=0.03) and IL-6 (P=0.002), increased expressions of TGF-β (P=0.04), and decreased expressions of NOXS (P<0.001), ROS (P<0.001) and NLRP3 (P=0.002). Treatment with swertiamarin and the NOXS inhibitor produced similar effects on the expressions of the inflammatory factors in the rat models (P>0.05). Conclusion DPN effectively relieves hyperalgesia in rat models of DPN by restoring the balance in the expressions of the inflammatory factors by suppressing NOXs/ROS/NLRP3 signaling pathway.

Key words: swertiposide; diabetic peripheral neuralgia; nucleotide-binding oligomerization domain-like receptor protein 3; nicotinamide adenine dinucleotide phosphate oxidase