摘要： 目的 观察氢气对链脲霉素致糖尿病周围神经病变模型大鼠坐骨神经功能和疼痛行为学的影响，并探讨其可能的作用机制。方法 腹腔注射链脲霉素（65 mg/kg）建立糖尿病大鼠模型，6 周后腹腔注射富氢生理盐水（5 ml/kg），连续治疗2 周后观察不同处理组大鼠坐骨神经功能和疼痛行为学变化，并检测坐骨神经炎性因子［肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）］及核因子-κB（NF-κB）p65 亚基表达变化。结果 （1）与正常对照组相比，模型制备成功第8 周时模型组大鼠体质量降低、血糖水平升高（均P = 0.000）；与模型组相比，氢气治疗组大鼠体质量和血糖水平无明显改善（均P > 0.05）。（2）与正常对照组相比，模型制备成功第8 周时模型组大鼠坐骨神经传导速度减慢、热痛阈和机械性痛阈降低（均P = 0.000）；而与模型组相比，氢气治疗后大鼠坐骨神经传导速度增加、热痛阈和机械性痛阈提高（均P = 0.000）。（3）经氢气治疗后，大鼠坐骨神经TNF-α和IL-6 表达水平降低（均P = 0.000），NF-κBp65 亚基阳性细胞数目减少（P = 0.000）。结论 糖尿病周围神经病变与炎症反应有关，而氢气可以通过抑制NF-κB 及其下游炎性因子的表达而发挥对糖尿病周围神经损害的保护作用。

关键词: 神经痛, 糖尿病神经病变, 氢, NF-κB, 肿瘤坏死因子α, 白细胞介素6, 疾病模型, 动物

Abstract: Objective  To investigate the effect of hydrogen on streptozotocin (STZ)-induced diabetic rat models with peripheral neuropathy and explore the possible mechanism.  Methods  Eighteen male Sprague-Dawley (SD) rats were randomly divided into model group (N = 6), hydrogen-treated group (N = 6) and normal control group (N = 6). After fasting for 12 h, experimental diabetic rat models were established by intraperitoneal injection of STZ (65 mg/kg of single dose), while normal control group only received a same dose of citrate buffer. Diabetes was confirmed with a fasting plasma glucose more than 16.67 mmol/L 48 h after STZ injection. After diabetic models were established successively, hydrogen-rich saline (5 ml/kg) was administered by intraperitoneal injection in hydrogen-treated group daily in 7th and 8th week after diabetes induction. Corresponding model and normal control groups received a same dose of normal saline. Changes of sciatic function and pain behavior in rats of different groups were measured to investigate the effect of hydrogen-rich saline. Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB) p65 expression were then determined to clarify the possible mechanism of hydrogen-mediated protection.  Results  1) Compared with normal control group, body weight in model group decreased significantly, while plasma glucose levels increased significantly (P = 0.000, for all) 8 weeks after STZ induction. Hydrogen did not show any effects on body weight and plasma glucose levels of treated rat models in comparison with model group (P = 0.256, 0.821).  2) Compared with normal control group, motor nerve conduction velocity (MNCV), heat pain threshold (HPT) and mechanical withdrawal threshold (MWT) decreased significantly in model group (P = 0.000, for all), but increased significantly in hydrogen-treated group when compared with model group in the 8th week (P = 0.000, for all).  3) Hydrogen also reduced the positively expressed cells of NF-κB p65 (P = 0.000) as well as levels of TNF-α and IL-6 (P = 0.000, for all).  Conclusion  Inflammation may participate and exaggerate painful diabetic neuropathy. Besides, hydrogen has the protective potential of ameliorating neuroinflammation and peripheral nerve injury by suppressing NF-κB pathway and its downstream inflammatory cytokines.

Key words: Neuralgia, Diabetic neuropathies, Hydrogen, NF-kappa B, Tumor necrosis factor-alpha, Interleukin-6, Disease models, animal