通心络胶囊抑制p38 MAPK磷酸化抑制糖尿病周围神经病变小鼠氧化应激  

Tongxinluo capsule inhibits oxidative stress in diabetic peripheral neuropathy mice by inhibiting the activity of p-p38 MAPK

作　　者：王超[1] 张会欣 邢邯英[1] 王杏[1] 刘敏[1] 张哲[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,河北石家庄050051 [2]河北以岭医药研究院药理室,河北石家庄050035

出　　处：《中国药理学通报》2015年第5期726-730,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项(No2011ZX09101-004-02);河北省中医药管理局科研计划项目(No 2014155)

摘　　要：目的观察通心络胶囊对糖尿病周围神经病变(DPN)小鼠氧化应激的作用并探讨其机制。方法 KK/Upj-Ay小鼠分为模型组、通心络高、中、低剂量组,另设C57BL/6小鼠为对照组。灌胃给药12周,测定热痛觉阈值和运动神经传导速度(MNCV);比色法测定血液中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;荧光定量PCR和Western blot测定坐骨神经血红素氧合酶-1(HO-1)、γ-谷氨酰半胱氨酸合成酶(γ-GCS)表达;Western blot测定坐骨神经p38 MAPK、p-p38 MAPK、JNK、p-JNK、ERK、p-ERK蛋白表达。结果与模型组比较,通心络组小鼠痛觉阈值升高,MNCV明显增快(P<0.05,P<0.01);SOD、GSH-Px活性明显上升,MDA含量上升(P<0.01);HO-1、γ-GCS mRNA和蛋白表达明显升高(P<0.05,P<0.01);p-p38 MAPK表达明显下降(P<0.05)。结论通心络胶囊可通过抑制p38 MAPK磷酸化水平而发挥其抗DPN小鼠氧化应激损伤的作用。Aim To investigate the effects of Tongxin-luo capsule on oxidative stress in diabetic peripheral neuropathy （DPN ）mice and its mechanisms.Meth-ods KK/Upj-Ay mice were divided into model, Tongxinluo low-dose group, Tongxinluo middle-dose group and Tongxinluo high-dose group.C57BL/6 mice were selected as control group.Mice were given drugs intragastrically for 12 weeks.Paw withdrawal latency, motor nerve conduction velocity （MNCV）were detec-ted.Activity of superoxide dismutase （SOD）,gluta-thione peroxidase （GSH-Px）and content of malondial-dehyde （MDA）in blood were detected by colorimetric method.The expression of heme oxygenase-1 （HO-1 ）,γ-glutamyl cysteine synthetase （γ-GCS ） of sciatic nerve was examined by real time PCR and Western blot.The protein expression of p38 MAPK,p-p38＆nbsp;MAPK,JNK,p-JNK,ERK,p-ERK was examined by Western blot.Results Compared with model group, paw withdrawal latency was increased and MNCV was faster in Tongxinluo group （P 〈0.05 ,P 〈0.0 1 ）. SOD and GSH-Px contents significantly increased, MDA content decreased （P 〈0.01 ）.HO-1,γ-GCS mRNA and protein expression significantly increased （P〈0.05,P 〈0.01 ）in Tongxinluo group.p-p38 MAPK protein expression decreased in Tongxinluo group （P〈0.05 ）.Conclusion Tongxinluo can in-hibit oxidative stress in DPN of mice via suppressing the phosphorylation of p38 MAPK.

关 键 词：通心络胶囊 糖尿病周围神经病变 氧化应激 MAPK p38 MAPK KK/Upj-Ay小鼠 

分 类 号：R-332[医药卫生] R287