摘要目的：评价富氢液对糖尿病神经痛大鼠外周神经核转录因子E2相关因子2（ Nrf?2）∕抗氧化反应原件（ ARE）通路的影响。方法健康雄性SD大鼠36只，8周龄，体重180～200 g，采用随机数字表法分为3组（ n＝12）：对照组（ C组）、糖尿病神经痛组（ DNP 组）和富氢液组（ HRS组）。DNP组与HRS组采用腹腔注射1％链脲佐菌素（ STZ）65 mg∕kg的方法制备糖尿病模型。 HRS组于注射STZ后14 d时腹腔注射富氢液5 ml∕kg，1次∕d，连续14 d，C组和DNP组注射等容量的生理盐水。于注射STZ前2 d（ T0）、注射后7、14、21和28 d（ T1?T4）时测定机械缩足反应阈（ MWT）和热缩足潜伏期（ TWL）。于T4痛阈测定结束后，测定右后肢运动神经传导速度（ MNCV）和神经传导潜伏期；取坐骨神经，采用Western blot法测定坐骨神经核蛋白Nrf?2、总蛋白血红素氧合酶1（ HO?1）、醌氧化还原酶1（ NQO1）的表达水平。结果与C组比较，DNP组和HRS组T1?T4时MWT降低，TWL缩短，坐骨神经核蛋白Nrf2、总蛋白HO?1、NQO1表达上调（P＜0．05）；与DNP 组比较，HRS组T3、T4时MWT升高，TWL延长，坐骨神经核蛋白Nrf2、总蛋白HO?1、NQO1表达上调（P＜0．05）。结论富氢液减轻大鼠糖尿病神经痛的机制与激活外周神经Nrf2∕ARE通路有关。

abstractsObjective To evaluate the effect of hydrogen?rich saline on nuclear factor erythroid 2?related factor 2 ( Nrf2)∕antioxidant response element ( ARE) pathway in the peripheral nerve in a rat model of diabetic neuropathic pain ( DNP ) . Methods Thirty?six healthy male Sprague?Dawley rats, aged 8 weeks, weighing 180-200 g, were randomly divided into 3 groups ( n=12 each) using a random number table: control group ( C group) , DNP group and hydrogen?rich saline group ( HRS group) . Diabetes melli?tus was produced by intraperitoneal 1% streptozocin ( STZ) 65 mg∕kg and confirmed by fasting blood glucose concentration>16?67 mmol∕L. Hydrogen?rich saline 5 ml∕kg was injected intraperitoneally once a day for 14 consecutive days starting from 14 days after STZ injection in group HRS, and the equal volume of normal saline was given in C and DNP groups. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 2 days before STZ injection ( T0 ) , and 7, 14, 21 and 28 days after STZ injection ( T1?4 ) . After measurement of the pain threshold at T4 , the motor nerve conduction velocity ( MNCV) of the right hindlimb and distal motor latency were measured. The expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was detected in the sciatic nerve by Western blot. Re?sults Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T1?4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in DNP and HRS groups (P<0?05). Compared with group DNP, the MWT was significantly increased, and the TWL was prolonged at T3 and T4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in group HRS ( P<0?05) . Conclusion The mechanism by which hydrogen?rich saline mitigates DNP is related to activated Nrf2∕ARE pathway in the peripheral nerve of rats.