TLR4抑制剂对糖尿病周围神经痛模型大鼠的治疗作用.docVIP

TLR4抑制剂对糖尿病周围神经痛模型大鼠的治疗作用 　　[摘要] 目的 探讨Toll样受体4（TLR4）抑制剂TAK-242对糖尿病周围神经痛（DPN）模型大鼠的治疗效果及其可能的作用机制。 方法 SPF级雄性SD大鼠60只，随机均分为3组，分别为正常对照组（NC组）、DPN模型组（DPN组）、TAK-242治疗组（TAK组）。采用链脲佐菌素（STZ）方法建立DPN大鼠模型，采用ELISA及RT-PCR方法检测DPN模型大鼠腰膨大脊髓组织的高迁移率族蛋白B1（HMGB1）-TLR4轴上下游基因（HMGB1、TLR4、MAPK、NF-κB、IL-6）的变化，分析上述细胞因子表达水平与大鼠疼痛行为的相关性。使用TLR4抑制剂TAK-242对DPN模型大鼠进行药物干预，观察其治疗效果及对HMGB1-TLR4轴基因表达的影响。 结果 ELISA检测显示，DPN组大鼠的血清HMGB1、TLR4、IL-6表达水平均较NC组升高（P中国论文网 /6/view-7216050.htm 　　[关键词] TLR4；TAK-242；HMGB1-TLR4；糖尿病周围神经痛 　　[中图分类号] R587.2 [文献标识码] A [文章编号] 1674-4721（2016）02（a）-0009-04 　　Therapeutic effect of TAK-242 on diabetic peripheral neuropathic pain rats 　　LU Yi1 YAO Jia-yin2 YAO Xin-hua1▲ QING Zhao-hui1 TONG Hui1 LIU Ling1 　　1.Department of Anesthesiology，Guangzhou Hospital of Traditional Chinese Medicine，Guangzhou 510130，China；2.Department of Gastroenterology，the Sixth Hospital Affiliated to Sun Yat-Sen University，Guangzhou 510655，China 　　[Abstract] Objective To investigate the therapeutic effect and possible mechanisms of TLR4 inhibitor named TAK-242 on the diabetic peripheral neuropathic （DPN） rat model. Methods 60 male SD rats with SPF level were randomly divided into 3 groups， such as normal control group （NC group）， DPN model group （DPN group），TAK-242 treatment group （TAK group）.DPN rat models were established by using the method of streptozocin （STZ），and behavior analysis were made.Expressions of HMGB1-TLR4 related genes such as HMGB1，TLR4，MAPK，NF-κB and interleukin-6 （IL-6） were determined by RT-PCR.Correlations of genes mentioned above and the pain behavior of rats were analyzed.TLR4 inhibitor named TAK-242 was used for drug intervention.Its therapeutic effect and the effect on the expressions of HMGB1-TLR4 axis were observed. Results There was a significant increase in the spontaneous behavior and decrease in the pain threshold of rats in DNP group compared with NC group （P 　　[Key words] TLR4；TAK-242；HMGB1-TLR4；Diabetic peripheral neuropathic 　　在糖尿病患者中约20%的患者合并有糖尿病周围神经病变，占糖尿病神经病变的50%[1-2]