氢气抑制核因子-κB通路对糖尿病周围神经病变的保护作用

Protective effect of hydrogen on diabetic peripheral neuropathy by suppressing nulcear factor-kappaB pathway

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(TNFα)和白细胞介素6(IL 6)]及核因子κB(NFκB)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TNFα和IL 6表达水平降低(均P=0.000),NFκB p65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NFκB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。

Objective To investigate the effect of hy drogen on streptozotocin(STZ) in duce d diabetic rat mo dels with peripheral neuropathy an d explore the possible mechanism.Metho dsEighteen male Sprague Dawley(SD) rats were ran domly divi de d into mo del group(N=6), hy drogen treate d group(N=6) an d normal control group(N = 6). After fasting for 12 h, experimental diabetic rat mo dels were establishe d by intraperitoneal injection of STZ(65 mg/kg of single dose), while normal control group only receive d a same dose of citrate buffer. Diabetes was confirme d with a fasting plasma glucose more than16.67 mmol/L 48 h after STZ injection. After diabetic mo dels were establishe d successively, hy drogen rich saline(5 ml/kg) was a dministere d by intraperitoneal injection in hy drogen treate d group daily in 7th an d 8th week after diabetes in duction. Correspon ding mo del an d normal control groups receive d a same dose of normal saline. Changes of sciatic function an d pain behavior in rats of different groups were measure d to investigate the effect of hy drogen rich saline. Proinflammatory cytokines, inclu ding tumor necrosis factor α(TNF α) an d interleukin 6(IL 6), an d nuclear factor kappaB(NF κB) p65 expression were then determine d to clarify the possible mechanism of hy drogen me diate d protection.Results1) Compare d with normal control group, bo dy weight in mo del group decrease d significantly, while plasma glucose levels increase d significantly(P = 0.000, for all) 8 weeks after STZ in duction. Hy drogen di d not show any effects on body weight an d plasma glucose levels of treate d rat mo dels in comparison with mo del group(P = 0.256, 0.821).2) Compare d with normal control group, motor nerve con duction velocity(MNCV), heat pain threshol d(HPT)an d mechanical with drawal threshol d(MWT) decrease d significantly in mo del group(P = 0.000, for all), butincrease d significantly in hy drogen treate d group when compare d with mo del group in the 8th week(P =0.000, for all). 3) Hy drogen also re duce d the positively expresse d cells of NF κB p65(P=0.000) as well as levels of TNF α an d IL 6(P = 0.000, for all).ConclusionInflammation may participate an d exaggerate painful diabetic neuropathy. Besi des, hy drogen has the protective potential of ameliorating neuroinflammation an d peripheral nerve injury by suppressing NF κB pathway an d its downstream inflammatory cytokines.