脊髓背角MCP-1-JAK2/STAT3信号转导参与大鼠2型糖尿病神经病理性痛的机制研究  

Mechanism of MCP-1-JAK2 / STAT3 signal transduction in spinal cord dorsal horn contributing to rats with type 2 diabetic neuropathic pain

作　　者：袁超[1] 管金川 曹红[1] 李军[1] 

机构地区：[1]温州医科大学附属第二医院麻醉科,浙江温州325000

出　　处：《中国病理生理杂志》2015年第8期1467-1471,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81073125);浙江省自然科学基金资助项目(No.Y2090252)

摘　　要：目的:探讨脊髓背角MCP-1-JAK2/STAT3信号转导是否参与大鼠2型糖尿病神经病理性疼痛(DNP)的形成与发展。方法:雄性SD大鼠高糖高脂饲养8周,通过腹腔单次注射链脲佐菌素(STZ)制备大鼠2型DNP模型。将2型DNP大鼠随机分为4组,每组16只:DNP组、DNP+MCP-1抑制剂组(DM组)、DNP+JAK2抑制剂AG490组(DA组)和溶剂对照组(SC组)。DA、DM和SC组分别于注射STZ 14 d后蛛网膜下腔置管,3 d后DM、DA和SC组分别给予MCP-1中和抗体10μL(0.1 mg/L)、AG490 10μL(1 mmol/L)和3.5%DMSO 10μL,每天1次,连续14 d。DNP组不做任何处理。另取16只大鼠为对照(control,C)组,普通饲料喂养。蛛网膜下腔给药后第1、3、7和14天时测定机械缩足阈值(MWT)和热缩足反射潜伏期(TWL),各组随机取4只大鼠处死,取L4-6脊髓膨大,采用Western blot法检测p-JAK2和p-STAT3的表达。结果:与C组比较,DNP和SC组第1、3、7和14天时MWT降低,TWL缩短,脊髓背角p-JAK2和p-STAT3表达上调(P<0.05);与DNP组比较,DM和DA组第1、3、7和14天时MWT升高和TWL延长,脊髓背角p-JAK2和p-STAT3表达下调(P<0.05);DNP组与SC组各指标比较差异无统计学意义。结论:脊髓背角MCP-1-JAK2/STAT3信号转导参与大鼠2型DNP的产生和维持。AIM： To explore whether MCP-1-JAK2 /STAT3 signal transduction in the spinal dorsal horn involves the formation and development of rat type 2 diabetic neuropathic pain（ DNP）. METHODS： The male SpragueDawley rats were fed with a high-fat and fructose diet for 8 weeks,and then received a single intraperitoneal streptozocin injection to prepare the type 2 DNP model. The type 2 DNP rats were randomly divided into 4 groups（ n = 16） ： DNP group,MCP-1 neutralizing（ DM） group,DNP ＋ AG490（ DA） group and solvent control（ SC） group. A catheter of PE-10 was placed into the subarachnoid space of the rats in groups DM,DA and SC. After 3 d,the rats in DM,DA and SC groups were injected with MCP-1 inhibitor 10 μL at 0. 1 mg / L,AG490 10 μL at 1 mmol / L and DMSO 10 μL at 3. 5% once a day for 14 days,respectively. Another 16 normal rats were selected as control（ C） group and were fed with common forage.The mechanical withdrawal threshold（ MWT） and thermal withdrawal latency（ TWL） were measured at 1,3,7 and 14 d after subarachnoid injection. The lumbar segments 4-6 of the spinal cord were removed at the same time for determination of the expressions of p-JAK2 and p-STAT3 by Western blot. RESULTS： Compared with C group,MWT was significantly decreased,TWL was shortened and the expression of p-JAK2 and p-STAT3 in the spinal dorsal horn was up-regulated at 1,3,7 and 14 d in DNP and SC groups（P〈0. 05）. Compared with DNP group,MWT was significantly increased,TWL was prolonged and the expression of p-JAK2 and p-STAT3 in spinal dorsal horn was down-regulated at 1,3,7 and 14 d in DM and DA groups（P〈0. 05）. No significant difference in the MWT,TWL and expression of p-JAK2 and p-STAT3 between DNP group and SC group was observed（P〈0. 05）. CONCLUSION： The MCP-1-JAK2 / STAT3 signal transduction in the spinal dorsal horn involves the formation and development of DNP in rats.

关 键 词：2型糖尿病 脊髓背角 单核细胞趋化蛋白1 JANUS激酶2 信号转导及转录激活因子3 

分 类 号：R363[医药卫生—病理学]