补阳还五汤抑制TLR4信号通路减轻db/db糖尿病小鼠周围神经病变炎症反应  

Buyang Huanwu decoction alleviates inflammatory response in mice with diabetic peripheral neuropathy through inhibiting TLR4 signaling pathway

作　　者：暴鹏[1] 李雪[1] 孙丽莎[1] 张晓冉[1] 杨欣怡 李朝敏[1] BAO Peng;LI Xue;SUN Lisha;ZHANG Xiaoran;YANG Xinyi;LI Chaomin(Department of Endocrinology,Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学附属医院内分泌科,成都610075

出　　处：《山西医科大学学报》2020年第2期153-157,共5页Journal of Shanxi Medical University

摘　　要：目的观察补阳还五汤对db/db糖尿病小鼠周围神经病变炎症反应中TLR4/MAPK/NF-κB信号通路以及炎症因子的作用,探讨其对周围神经小鼠炎症损伤的保护机制。方法将50只db/db小鼠随机分成5组:空白对照组、模型组、补阳还五汤低、中、高剂量组[1.6,3.2,6.4 g/(kg·d)],每组10只。空白对照和模型组以10 ml/kg体质量的去离子水灌胃,各给药组小鼠均以10 ml/kg体质量相应浓度的药物灌胃,每日1次,连续84 d。第84天最后一次给药后,检测小鼠足底热敏反应时间,采用ELISA法检测小鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及IL-1β的表达水平,采用Western blot法检测小鼠背根神经节中TLR4、p38 MAPK、p-P38、IκB-α、P65、p-IκB-α和p-P65的表达量。结果与空白对照组相比,模型组小鼠足底热敏反应时间显著增加(P<0.05),其血清中IL-6、IL-1β和TNF-α及背根神经节中TLR4、p-P38、p-IκB-α和p-P65蛋白的表达水平也显著增强,差异具有统计学意义(P<0.05)。与模型组对比,各给药组能显著缩短小鼠足底热敏反应时间(P<0.05);血清中IL-6、IL-1β和TNF-α及背根神经节中TLR4、p-P38、p-IκB-α和p-P65表达水平下调(P<0.05)。随着剂量的增加,db/db小鼠热敏反应时间及相关炎性因子的表达水平相应降低,其中以高剂量组db/db小鼠减少较为显著。结论补阳还五汤可通过抑制TLR4、p38 MAPK及NF-κB信号转导通路的异常激活,缓解db/db糖尿病小鼠周围神经病变的炎症反应,从而保护周围神经的功能。Objective To investigate the effect of Buyang Huanwu decoction on TLR4/MAPK/NF-κB signaling pathways and inflammatory factors in diabetic peripheral neuropathy model mice(db/db mice),and to explore its protective mechanism against inflammatory damage of peripheral nerve in db/db mice.Methods Fifty db/db mice were randomly divided into 5 groups:blank control group,model group,Buyang Huanwu decoction low-dose,medium-dose and high-dose groups[1.6,3.2,6.4 g/(kg·d)],with 10 mice in each group.The mice in Buyang Huanwu decoction groups were intragastrically given corresponding dose of Buyang Huanwu decoction with 10 ml of deionized water per kilogram of body weight once a day for consecutive 84 d,and the mice in blank control group and model group were intragastrically given deionized water with 10 ml of deionized water per kilogram of body weight.After the last admi-nistration,the heat reaction time of the sole of the foot was measured and the tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1βin the serum of the mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression levels of TLR4,p38 MAPK and p-P38,IκB-α,P65 and p-IκB-α,p-P65 in the dorsal root ganglia of mice were detected by Western blotting assay.Results Compared with blank control group,the plantar thermo-sensitive response time was significantly prolonged in model group(P<0.05),the expression levels of IL-6,IL-1β and TNF-α in serum and the TLR4,p-P38 p-IκB-α and p-P65 proteins in dorsal root ganglia were also significantly enhanced(P<0.05).Compared with model group,the plantar thermo-sensitive response time in Buyang Huanwu decoction groups was shortened significantly(P<0.05),and the expression levels of IL-6,IL-1β,TNF-α in serum,and TLR4,p-P38,p-IκB-αand p-P65 in dorsal root ganglia were down-regulated(P<0.05).With the increase of the dose,the thermal response time and the expression level of related inflammatory factors in db/db mice decreased,especially in high-dose group.Conclusion Buyang Huanwu decoction can

关 键 词：补阳还五汤 TLR4/MAPK/NF-κB信号转导通路 糖尿病周围神经病变 炎症因子 

分 类 号：R285.5[医药卫生—中药学]