RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究

doi:10.12047/j.cjap.5521.2017.067

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (3): 277-281.doi: 10.12047/j.cjap.5521.2017.067

RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究

马益梅, 李传达, 朱雅冰, 徐霞, 李军, 曹红

温州医科大学附属第二医院麻醉科, 浙江温州 325027

收稿日期:2016-11-14 修回日期:2017-02-20 出版日期:2017-05-28 发布日期:2018-06-20
通讯作者: 曹红,Tel:13758497562,E-mail:caohongwz@163.com E-mail:caohongwz@163.com
基金资助:
国家自然科学基金（81073125）

The mechanism of RvD1 alleviates type 2 diabetic neuropathic pain by influencing microglia polarization in rats

MA Yi-mei, LI Chuan-da, ZHU Ya-bing, XU Xia, LI Jun, CAO Hong

Department of Anesthesiology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China

Received:2016-11-14 Revised:2017-02-20 Online:2017-05-28 Published:2018-06-20
Supported by:
国家自然科学基金（81073125）

摘要/Abstract

摘要： 目的：采用2型糖尿病神经病理性痛大鼠，探讨其脊髓背角小胶质细胞极化情况以及消退素D1（RvD1）缓解大鼠2型糖尿病神经病理性痛的机制。方法：雄性SD大鼠高糖高脂饲养，腹腔注射链脲佐菌素（STZ），制备大鼠2型糖尿病神经病理性痛模型。将2型糖尿病神经病理性痛大鼠随机分为3组（n=36）：2型糖尿病神经病理性痛组（D组）、2型糖尿病神经病理性痛注射RvD1组（R组）和溶剂对照组（S组）。R、S组分别于注射STZ 14 d后蛛网膜下腔置管，3 d后R、S组分别给予RvD1 10μl（10 ng/μl）和100%乙醇10μl，每天1次，连续14 d，D组不做任何处理。另取36只正常大鼠为正常对照组（N组），普通饲料喂养。鞘内给药后第1、3、7、14天时测定机械缩足阈值（MWT）和热缩足潜伏期（TWL），各组随机取9只大鼠处死，取L4-6脊髓膨大，采用Western blot法检测小胶质细胞M1、M2型极化标记物，即诱导型一氧化氮合酶（iNOS）、精氨酸酶1（Arg1）的表达。结果：与N组比较，D、S组第1、3、7、14天时MWT降低、TWL缩短，脊髓背角Arg1表达减少，iNOS表达增多（P < 0.05）；与D组比较，R组第7、14天时MWT升高、TWL延长，脊髓背角Arg1表达增多，iNOS表达减少（P < 0.05）；D组与S组各指标比较差异无统计学意义。结论：RvD1促进小胶质细胞M2型极化并缓解大鼠2型糖尿病神经病理性痛。

关键词: 大鼠, 2型糖尿病, 脊髓, 小胶质细胞极化, RvD1, Arg1, iNOS

Abstract: Objective: To study the relationship between microglia polarization in the spinal dorsal horn and type 2 diabetic neuropathic pain (DNP). And explore the mechanism of RvD1 alleviating type 2 diabetic neuropathic pain. Methods: Type 2 diabetes mellitus (T2DM) rats came from the male SD rats which were fed by high-fat and high-sucrose diet and given intraperitoneal streptozotocin(STZ), then detected fa sting blood glucose level, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), which was to prepare the type 2 DNP model rats. And they were randomly divided into 3 groups:type 2 DNP group (group D), type 2 DNP and RvD1 group (group R), type 2 DNP and solvent control group (group S), 36 rats in each group. After being given STZ 14 days, the rats of group D, R, S were placed a catheter in subarachnoid cavity. Three days later, the RvD1 10μl (10 ng/μl) and 100% ethanol 10μl were injected into subarach-noid cavity through the catheter once a day for 14 consecutive days. Another 36 normal rats were served as normal control group (group N) and were fed with common forage. MWT and TWL were measured at 1, 3, 7, 14 days after Subarachnoid injection, then the nine rats'spinal cord of the lumbar segment 4~6 were removed to detect the expression of inducible nitric oxide synthase(iNOS) and arginase 1(Arg1) by Western blot, the marker of microglia M1 and M2 polarization. Results: Compared with group N, MWT was decreased significantly and TWL was shortened, the expression of Arg1 was down-regulated and the expression of iNOS was up-regulated in spinal dorsal horn at the 1, 3, 7, 14 days in groups D and S (P < 0.05). Compared with group D, MWT was significantly increased and TWL was prolonged, the expression of Arg1 was up-regulated and the expression of iNOS was down-regulated in spinal dorsal horn at the 7, 14 days in group R (P < 0.05). There was no significant difference in the MWT, TWL and expression of Arg1 and iNOS between D and S groups. Conclusion: RvD1 promotes mi-croglia toward M2 polarization and alleviates type 2 diabetic neuropathic pain in rats.

Key words: rats, T2DM, the spinal dorsal horn, microglia polarization, RvD1, Arg1, iNOS

马益梅, 李传达, 朱雅冰, 徐霞, 李军, 曹红. RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究[J]. 中国应用生理学杂志, 2017, 33(3): 277-281.

MA Yi-mei, LI Chuan-da, ZHU Ya-bing, XU Xia, LI Jun, CAO Hong. The mechanism of RvD1 alleviates type 2 diabetic neuropathic pain by influencing microglia polarization in rats[J]. CJAP, 2017, 33(3): 277-281.

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RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究

The mechanism of RvD1 alleviates type 2 diabetic neuropathic pain by influencing microglia polarization in rats

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