基于TLR4/MyD88/NF-κB通路探究桃红四物汤对糖尿病周围神经病变大鼠炎症反应的影响

Effect of Taohong Siwu decoction on inflammatory response in diabetic peripheral neuropathy rats based on TLR4/MyD88/NF-κB pathway

目的:探究桃红四物汤对糖尿病周围神经病变(DPN)大鼠炎症反应及对Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子kappan B(NF-κB)通路的影响。方法:从45只SD大鼠中随机选取10只为对照组,其余35只大鼠建立DPN模型,3只大鼠建模失败,其余随机分为模型组,桃红四物汤低、高剂量组及α-硫辛酸组,每组各8只。桃红四物汤低、高剂量组分别给予4.5、18 g/(kg·d)的桃红四物汤,α-硫辛酸组给予α-硫辛酸20 mg/(kg·d),对照组及模型组给予等量的0.9%氯化钠溶液,均灌胃给药。连续给药8周后,检测大鼠血清炎症因子、血糖及血脂指标及神经传导情况,观察坐骨神经病理学变化,检测TLR4相关通路蛋白表达情况。结果:与对照组比较,模型组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及白细胞介素-6(IL-6)水平升高,血糖、糖化血红蛋白(HbA1c)、甘油三酯(TG)及血清总胆固醇(TC)水平升高,感觉神经传导速度(SNCV)及运动神经传导速度(MNCV)水平降低,TLR4、MyD88、NF-κB蛋白表达上调(P<0.05);与模型组比较,桃红四物汤低、高剂量组及α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05);与桃红四物汤低剂量组比较,桃红四物汤高剂量组及α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05);与桃红四物汤高剂量组比较,α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05)。结论:桃红四物汤能够改善DPN大鼠炎症反应指标及血糖血脂水平,提高神经传导速度,对坐骨神经起到保护作用,其作用机制可能与抑制TLR4/MyD88/NF-κB通路有关。

Objective:To explore the effect of Taohong Siwu decoction on inflammatory response and TLR4/MyD88/NF-κB pathway in diabetic peripheral neuropathy(DPN)rats.Methods:Ten rats were randomly selected from 45 SD rats as the control group,and the remaining 35 rats were used to establish the DPN model.Three rats failed to establish the model,and the rest were randomly divided into four groups:model group,low-dose and high-dose Taohong Siwu decoction group,andα-lipoic acid group,with eight rats in each group.The low-dose and high-dose groups were given 4.5,18 g/(kg·d)of Taohong Siwu decoction respectively,theα-lipoic acid group was given 20 mg/(kg·d)ofα-lipoic acid,and the control group and model group were given equal amounts of saline,all by gavage.After continuous administration for 8 weeks,serum inflammatory factors,blood glucose and blood lipid indicators,nerve conduction status were detected in rats.The pathological changes of sciatic nerve were observed,and the expression of TLR4-related pathway proteins was detected.Results:Compared with the control group,serum TNF-α,IL-1βand IL-6 levels increased in model group,blood glucose,HbA1c,TG and TC levels increased,SNCV and MNCV levels decreased,TLR4,MyD88,NF-κB protein expression up-regulated(P<0.05).Compared with model group,serum TNF-α,IL-1β,IL-6 levels decreased in low-dose,high-dose Taohong Siwu decoction groups,andα-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Compared with low-dose Taohong Siwu decoction group,serum TNF-α,IL-1β,IL-6 levels decreased in high-dose Taohong Siwu decoction groups,andα-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Compared with high-dose Taohong Siwu decoction groups,serum TNF-α,IL-1β,IL-6 levels decreased inα-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Conclusion:Taohong Siwu decoction can improve inflammatory response indicators,blood glucose and blood lipid levels in DPN rats,increase nerve conduction velocity,protect sciatic nerve,which may be related to TLR4/MyD88/NF-κB pathway.