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

作　　者：马益梅 李传达 朱雅冰 徐霞[1] 李军[1] 曹红[1] 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, Chin)

机构地区：[1]温州医科大学附属第二医院麻醉科,浙江温州325027

出　　处：《中国应用生理学杂志》2017年第3期277-281,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金(81073125)

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(Rv D1)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Rv D1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Rv D1 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:Rv D1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。Objective： To study the relationship between micmglia polarization in the spinal dorsal horn and type 2 diabetic neuropathic pain （DNP）. And explore the mechanism of RvD1 alleviating type 2 diabetic neumpathie 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 fasting 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 SIZ 14 days, the rots of group D, R, S were placed a catheter in subarachnoid cavity. Three days later, the RvD1 10μl （ 10 ng/μl） and 100% ethanol 10 pl were injected into subarachnoid 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 l（Argl） 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 Argl 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 Argl 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 Argl and iNOS between

关 键 词：大鼠 2型糖尿病 脊髓 小胶质细胞极化 RvD1 Arg1 INOS 

分 类 号：R614[医药卫生—麻醉学]