| 糖络宁对DPN中IRE1-TRAF2-XBP-1途径的影响 |
| 投稿时间：2018-01-05 修订日期：2018-01-24 点此下载全文 |
| 引用本文：李潇,王婷婷,杨鑫伟,姚伟洁,朱笳悦,林娜,许利平.糖络宁对DPN中IRE1-TRAF2-XBP-1途径的影响[J].医学研究杂志,2018,47(11):33-40 |
| DOI：
10.11969/j.issn.1673-548X.2018.11.009 |
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| 作者 | 单位 | E-mail | | 李潇 | 100069 北京, 首都医科大学中医药学院 | | | 王婷婷 | 100069 北京, 首都医科大学中医药学院 | | | 杨鑫伟 | 100069 北京, 首都医科大学中医药学院
100069 北京, 首都医科大学中医络病研究北京重点实验室 | yxw0226@ccmu.edu.cn | | 姚伟洁 | 100069 北京, 首都医科大学中医药学院
100069 北京, 首都医科大学中医络病研究北京重点实验室 | | | 朱笳悦 | 100069 北京, 首都医科大学中医药学院
100069 北京, 首都医科大学中医络病研究北京重点实验室 | | | 林娜 | 100069 北京, 首都医科大学中国中医科学院中药研究所 | | | 许利平 | 100069 北京, 首都医科大学中医药学院
100069 北京, 首都医科大学中医络病研究北京重点实验室 | xulp@ccmu.edu.cn |
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| 基金项目:国家自然科学基金资助项目（面上项目）（81473142）；2016年北京高等学校高水平人才交叉培养"实培计划"项目（科研类363） |
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| 中文摘要:目的 探讨糖络宁对糖尿病周围神经病变（DPN）大鼠内质网应激IRE1-TRAF2-XBP-1途径的影响。方法 以高脂饲料联合链脲佐菌素诱导SD大鼠致DPN模型，经糖络宁干预12周后，采用苏木精-伊红（HE）染色法观察大鼠坐骨神经形态的变化，采用免疫荧光法检测DPN大鼠坐骨神经EDEM、PDI和TRAF2 蛋白表达，采用Western blot法检测DPN大鼠坐骨神经细胞凋亡途径P-JNK和caspase-3的蛋白表达。选用RSC96细胞株，采用高糖环境培养的施万细胞模型，用糖络宁含药血清分别干预24h和48h，采用高内涵分析方法分别测定糖络宁含药血清对施万细胞中EDEM、PDI、TRAF2和P-JNK蛋白表达的影响。结果 HE染色结果显示，模型组大鼠坐骨神经髓神经脱髓鞘严重；糖络宁低、高剂量组坐骨神经脱髓鞘现象得到改善，坐骨神经髓鞘积分吸光度显示，模型组比空白组明显降低（P<0.05），糖络宁高剂量组得到明显改善（P<0.05）；免疫荧光结果显示，糖络宁高低剂量组能使EDEM和PDI表达增加（P<0.01，P<0.05），TRAF2表达降低（P<0.01，P<0.05）；Western blot法检测结果显示，糖络宁高低剂量均显示P-JNK和caspase-3的表达降低。细胞实验中，24h和48h干预后的150mmol/L葡萄糖组EDEM与PDI显著性降低（P<0.01），TRAF2与P-JNK显著性升高（P<0.01）；高糖高剂量组的EDEM在24h干预后的表达显著升高（P<0.01），而P-JNK表达显著降低（P<0.05）；PDI在48h干预后的表达显著升高（P<0.01）；高糖高、低剂量组的TRAF2在24h和48h干预后均显著降低（P<0.01）。结论 糖络宁能够改善受损的坐骨神经结构，与糖络宁影响内质网应激相关IRE1-TRAF2-JNK途径相关，通过促进EDEM和PDI的表达，抑制TRAF2、P-JNK和caspase-3的表达，从而抑制神经细胞凋亡，改善DPN。 |
| 中文关键词:糖络宁 糖尿病周围神经病变 内质网应激 IRE1-TRAF2-XBP-1途径 施万细胞 |
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| Effect of Tangluoning on IRE1-TRAF2-XBP-1 Pathway of DPN |
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| Abstract:Objective To explore the effect of Tangluoning (TLN) in the IRE1-TRAF2-XBP-1 pathway in diabetic peripheral neuropathy (DPN) model rats. Methods In vivo, diabetic rats induced by streptozocin were usded as animal models for DPN and treated for 12 weeks. Hematoxylin-eosin staining was used to observe nerve pathology. Immunohistochemistry was used to detect the expression of the ER degradation enhancing mannosidase like protein (EDEM),protein disulfide isomerase (PDI) and Tumor necrosis factor receptor-associated factor2 (TRAF2). Western blot analysis was used to assess P-JNK and caspase-3 in the IRE1 pathway. High glucose incubated Schwann cells (SCs) were used as cell models and treated for 24h and 48h.HTS method was used to analyse the amount of EDEM, PDI, TRAF2 and P-JNK separately. Results Compared with the control group,the arrangement of sciatic nerve myelinated fibers was disordered,demyelination was serious, EDEM and PDI was decreased in Model group and TRAF2,P-JNK and caspase-3 was increased in Model group (P<0.05). Compared with the model group,the situation of inordinate sciatic nerve myelinated fibers arrangement and demyelination was improved in LTLN group and HTLN group, the expression of EDEM and PDI increased in LTLN group and in HTLN group (P<0.01),the expression of TRAF2,P-JNK and caspase-3 in HTLN group decreased (P<0.05). Compared with 25mmol/L glucose group, EDEM and PDI dropped significantly (P<0.01), and TRAF2 and P-JNK were significantly increased in 24h and 48h 150mmol/L glucose group. EDEM is significantly increased (P<0.01) in 24h 150mmol/L glucose+ 10%TLN group, PDI highly raised (P<0.01) in 48h 150mmol/L glucose+ 10%TNL group, P-JNK decreased in 24h 150mmol/L glucose+ 10%TLN group. Conclusion TLN significantly improves morphological structure and neurological function by reducing demyelination and improves the situation of inordinate sciatic nerve myelinated fibers arrangement because TLN has an impact on ER stress. TLN can enhance the expression of EDEM and PDI, down-regulate TRAF2,P-JNK and caspase-3 in IRE1-TRAF2-JNK pathway, inhibit apoptosis and ameliorates peripheral neuropathy in diabetic rats. |
| keywords:Tangluoning Diabetic peripheral neuropathy Endoplasmic reticulum stress IRE1-TRAF2-XBP-1 pathway Schwann cell |
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