糖络宁对糖尿病周围神经病变大鼠Nrf2/ARE通路的影响

Effect of Tangluoning on Nrf2/ARE pathway model rats with diabetic peripheral neuropathy

目的探讨糖络宁对糖尿病周围神经病变(DPN)大鼠Nrf2/ARE通路相关蛋白的影响。方法将SD雄性大鼠随机分为空白对照组和链脲佐菌素(STZ)组,STZ组大鼠一次性腹腔注射60 mg/kg STZ,造模1周后,将空腹血糖浓度≥16.7 mmol/L的大鼠稳定1个月后,随机分为模型对照组、α-硫辛酸组、糖络宁低剂量组和糖络宁高剂量组,并给予相应药物12周。麻醉取大鼠坐骨神经,采用免疫组织化学方法检测大鼠坐骨神经Kelch样环氧氯丙烷相关蛋白-1(Keap1),核转录因子NF-E2相关因子(Nrf2)、血红素加氧酶1(HO-1)、及谷氨酰半胱氨酸合成酶(γ-GCS)的表达。结果与空白对照组比较,模型对照组大鼠坐骨神经髓神经纤维排列紊乱,脱髓鞘严重,坐骨神经中Keap1、Nrf2、HO-1和γ-GCS的表达增加,差异有统计学意义(P<0.05);与模型对照组比较,糖络宁低、高剂量组大鼠坐骨神经髓神经纤维排列紊乱和脱髓鞘现象得到改善,其中糖络宁低剂量组Keap1、Nrf2表达增加,糖络宁高剂量组HO-1、γ-GCS表达增加,差异均有统计学意义(P<0.05)。结论糖络宁能够改善DPN大鼠坐骨神经的病理状态,上调Nrf2/ARE信号通路中Keap1、Nrf2、HO-1及γ-GCS的表达,增强机体抗氧化应激的能力。

Objective To explore the effect of Tangluoning（ TLN） on related proteins in the Nrf2/ARE pathway in diabetic peripheral neuropathy（ DPN） model rats. Methods SD male rats were randomly divided into the control group and streptozotocin（ STZ） group. STZ（ 60 mg/kg） group was injected intraperitoneally with STZ. After modeling for 1 week,rats with fasting blood glucose（ ≥16. 7 mmol·L^（-1）） stable for month were divided into the model control group,α-lipoic acid（ ALA） group,TLN low-dose group（ LTLN） and TLN high dose group（ HTLN）. After intragastric administration for 12 weeks,sciatic nerve of rats were taken off with anesthesia,then immunohistochemistry was used to detect the expression of the Kelch-like ECH-associated protein 1（ Keap1）,nuclear factor erythroid 2-related factor 2（ Nrf2）,heme oxygenase-1（ HO-1）,and γ-glutamylcysteine synthetase（ γ-GCS）. Results Compared with the control group,the arrangement of sciatic nerve myelinated fibers was disordered,demyelination was serious,the expression of Keap1,Nrf2,HO-1 and γ-GCS in sciatic nerve increased in the model group,the differences were statiscally significant（ P〈0. 05）. Compared with the model group,the situation of inordinate sciatic nerve myelinated fibers arrangement and demyelination was improved in LTLN group and HTLN group,the expression of Keap1 and Nrf2 increased in LTLN group,the expression of HO-1and γ-GCS in HTLN group increased obviously,the differences were statiscally significant（ P〈0. 05）. Conclusion TLN can improve the pathological state of sciatic nerve in DPN rats,enhance the expression of Keap1,Nrf2,HO-1 and γ-GCS in the Nrf2/ARE pathway,and strengthen the ability of oxidative stress of the body.