探讨白介素-6对糖尿病周围神经病变的干预性作用及机制

目的探讨白介素-6(interleukin-6,IL-6)对糖尿病周围神经病变大鼠的干预性作用及可能的机制。方法选取2015年10月至2018年12月80只健康雄性wistar大鼠作为研究对象,随机分为对照组、糖尿病非干预组、糖尿病低剂量IL-6干预组(1μg/kg,每周3次,皮下注射)和糖尿病高剂量IL-6干预组(10μg/kg,每周3次,皮下注射),每组20只。糖尿病大鼠造模应用尾静脉注射链脲菌素45 mg/kg方法,随机血糖>16.7 mmol/L为造模成功。检测各组大鼠外周血IL-6、腓肠神经形态学改变,以及腓肠神经NF-κB、I?Bα、IL-6mRNA及蛋白表达。结果糖尿病大鼠的糖化血红蛋白、血IL-6水平、腓肠神经IL-6、NF-κB、I?Bα表达水平均高于对照组,差异有统计学意义(P<0.05)。腓肠神经病理可见纤维密度减少,截面积减小,呈萎缩趋势,可见少量异常有髓纤维。应用IL-6干预后大鼠的腓肠神经病理改变较非干预组明显改善,且IL-6,NF-κB,I?Bα的mRNA及蛋白表达水平低于非干预组,高剂量IL-6干预后上述炎症因子的表达与非干预组比较差异有统计学意义(P<0.05)。结论 IL-6可通过抑制腓肠神经NF-κB的表达,缓解糖尿病大鼠周围神经病变的进展。

To explore the interventional effect and mechanism of interleukin-6 on diabetic peripheral neuropathy

Objective To investigate the interventional effect of interleukin-6(IL-6) on diabetic peripheral neuropathy rats and its possible mechanism. Methods 80 healthy male wistar rats from October 2015 to December 2018 were selected as research subjects and they were randomly divided into control group, diabetic non-intervention group, low-dose IL-6 intervention group(1 μg/kg, 3 times/week, subcutaneous injection), and high-dose IL-6 intervention group(10 μg/kg, 3 times/week, subcutaneous injection), with 20 cases in each group. The model of diabetic rats was made by injecting streptozotocin(STZ) 45 mg/kg, with random blood glucose of >16.7 mmol/L. After 4 weeks of IL-6 intervention, We detected the changes of IL-6 in peripheral blood, changes in sural neuropathy, and the NF-κB, I?Bα, IL-6 mRNA and protein expression of sural nerve in each group. Results The hemoglobin A1 c, blood IL-6 level, sural nerve IL-6, NF-κB, I?Bα expression were higher than those of the control group,the difference was statistically significant(P<0.05), the pathology of sural nerve showed decreased fiber density, decreased cross-sectional area, and atrophy trend, with a small number of abnormal myelinated fibers. After IL-6 intervention, the pathological image of sural nerve were improved compared with those in the non-intervention group, IL-6, NF-κB, I?B mRNA and protein expression level decreased compared with the non-intervention group. After the intervention of high dose of IL-6, the expression of these inflammatory factors was statistically different from that of the non-intervention group(P<0.05). Conclusion IL-6 inhibits the expression of NF-κB in the sural nerve and alleviates the progression of peripheral neuropathy in diabetic rats.