摘要目的：评价脊髓单核细胞趋化蛋白?1（ MCP?1）?细胞外信号调节激酶（ ERK）?驱动蛋白超家族17（ KIF17）∕含2B亚基的N?甲基?D?天冬氨酸受体（ NR2B）信号通路在大鼠2型糖尿病神经痛维持中的作用。方法高脂高糖喂养6周龄雄性SD大鼠（体重120～160 g）8周诱发胰岛素抵抗，单次腹腔注射1％链脲佐菌素（STZ）35 mg∕kg，3 d后空腹血糖≥16．7 mmol∕L为2型糖尿病模型制备成功。注射STZ 14 d时机械缩足阈（ MWT）和热缩足潜伏期（ TWL）下降至基础值的85％以下为2型糖尿病神经痛模型制备成功。采用随机数字表法，将2型糖尿病神经痛大鼠分为4组（ n＝36）：2型糖尿病神经痛组（ DNP组）、2型糖尿病神经痛＋MCP?1中和抗体组（ DM组）、2型糖尿病神经痛＋ERK抑制剂U0126组（ DE组）和2型糖尿病神经痛＋5％二甲基亚砜组（ DD组）。 DM组、DE组和DD组分别于注射STZ 14 d时鞘内注射0．1 ng∕μl MCP?1中和抗体、0．5μg∕μl U0126和5％二甲基亚砜各10μl，1次∕d，连续注射14 d。取36只大鼠喂以普通饲料作为正常对照组（ C组）。分别于注射STZ前及鞘内给药1、3、7、14 d（ T0～4）时测定MWT和TWL；并于T1～4时测定痛阈后，每组处死9只大鼠，取脊髓组织，采用Western blot法测定磷酸化ERK（ p?ERK）、KIF?17和磷酸化NR2B（ p?NR2B）的表达水平。结果与C组比较，DNP 组、DM组、DE组和DD组T1～4时MWT降低，TWL缩短，脊髓组织p?ERK、KIF17和p?NR2B的表达上调（ P＜0．05）；与DNP组比较，DM组T3～4时、DE组T2～4时MWT升高，TWL延长，DM组和DE组T2～4时脊髓组织p?ERK、KIF17和p?NR2B的表达下调（ P＜0．05），DD组上述各指标差异无统计学意义（ P＞0．05）。结论脊髓MCP?1?ERK?KIF17∕NR2B信号通路参与了大鼠2型糖尿病神经痛的维持。

abstractsObjective To explore the role of spinal monocyte chemoattractant protein?1 ( MCP?1) ?extracellular signal?regulated protein kinase ( ERK)?kinesin superfamily motor protein 17 ( KIF17)∕N?methyl?D?aspartate receptor subunit 2B ( NR2B) signaling pathway in the maintenance of type 2 diabetic neuropathic pain (DNP) in rats. Methods Type 2 diabetes mellitus was induced by a high?fat and high?sucrose diet and intraperitoneal streptozotocin ( STZ) 35 mg∕kg, and confirmed by fasting blood glucose level≥16?7 mmol∕L 3 days later in male Sprague?Dawley rats aged 6 weeks. Type 2 DNP was confirmed when the mechanical paw withdrawal threshold ( MWT ) and thermal paw withdrawl latency ( TWL ) measured on day 14 after STZ administration decreased to< 80% of the baseline value. The rats with type 2 DNP were randomly divided into 4 groups ( n=36 each) using a random number table: type 2 DNP group&nbsp;(group DNP), type 2 DNP +MCP?1 neutralizing antibody group (group DM), type 2 DNP +ERK inhibi?tor group (group DE) and type 2 DNP + dimethyl sulfoxide group ( group DD). In DM, DE and DD groups, 0?1 ng∕μl MCP?1 neutralizing antibody 10 μl, 0?5 μg∕μl U0126 10 μl and 5 % dimethyl sulfoxide 10 μl were injected intrathecally, respectively, once a day for 14 consecutive days starting from 14 days after administration of STZ. Another 36 normal rats fed a common forage diet were adopted as con?trol group ( group C) . MWT and TWL were measured before STZ injection and at 1, 3, 7 and 14 days after STZ injection ( T0-4 ) . Nine rats were sacrificed after measurement of pain thresholds at T1-4 , and the lumbar segments ( L4-6 ) of the spinal cord were removed for determination of the expression of phosphoryla?ted ERK (p?ERK), KIF17 and phosphorylated NR2B (p?NR2B) by Western blot. Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, and the expression of p?ERK, KIF17 and p?NR2B was up?regulated at T1-4 in DNP, DM, DE and DD groups. Compared with group DNP, the MWT at T3-4 in group DM and at T2-4 in group DE was significantly increased, the TWL at T3-4 in group DM and at T2-4 in group DE was prolonged, and the expression of p?ERK, KIF17 and p?NR2B was down?regulated at T2-4 in DM and DE groups, and no significant changes were found in the pa?rameters mentioned above in group DD. Conclusion Spinal MCP?1?ERK?KIF17∕NR2B signaling pathway is involved in the maintenance of type 2 DNP in rats.