加巴喷丁对糖尿病神经病理痛大鼠背根神经节磷酸化信号转导和转录激活因子3表达的影响

摘要

目的：观察加巴喷丁（gabapentin， GBP）对糖尿病神经病理痛大鼠背根神经节磷酸化信号转导和转录激活因子3（p-STAT3）表达的影响。方法80只成年健康雄性SD大鼠，随机分为正常组（Control 组）、糖尿病神经病理痛组（ DNP组）、生理盐水＋DNP组（ SC＋DNP组）和加巴喷丁＋DNP组（ GBP＋DNP组），每组20只。采用链脲佐菌素（STZ）诱导的糖尿病神经病理痛大鼠模型；SC＋DNP组和GBP＋DNP组于STZ注射15天起分别腹腔注射生理盐水或GBP 50 mg/kg，1次/d，连续7天；采用行为学测试测定STZ注射前1天及注射后3、7、10、14、21、28天大鼠缩足反射机械刺激阈值（PWMT）和缩足反射热辐射潜伏期（PWTL），免疫组化方法检测大鼠背根神经节（DRG）中p-STAT3的表达。结果与Control 组比较， DNP组PWMT〔（3．8±0．84） g〕降低、PWTL〔（5．9±0．94） s〕缩短，DRG中p-STAT3蛋白的表达上调（P＜0．05）；与DNP组比较， SC＋DNP组大鼠在腹腔注射生理盐水后，PWMT〔（4．03±0．5） g〕、PWTL〔（6．2±0．7） s〕和p-STAT3蛋白的表达无明显改变（P＞0．05）；与DNP组和SC＋DNP组比较， GBP＋DNP组PWMT〔（8．4±0．87） g〕升高，PWTL〔（10±1．2） s〕延长， DRG中p-STAT3蛋白的表达下调（P＜0．05）。结论 GBP能减轻大鼠糖尿病神经病理痛，其机制可能与抑制p-STAT3的表达水平有关。%Objective To investigate the effects of gabapentin on the expression of p -STAT3 in dorsal root ganglia of a rat model of diabetic neuropathological pain ( DNP) .Methods 80 male SD rats weighing 200-220 g were randomly divided into 4groups (20 in each):a control group, a DNP group, a saline (SC+DNP) group and a gabapentin (GBP+DNP) group.Then a rat model of diabetic neuropathological pain was established through injection of streptozocin ( STZ) .Fifteen days after STZ administration , the rats of the SC+DNP and GBP+DNP groups were intraperitonealy in-jected with normal saline and 50 mg/kg GBP, respectively, once per day for seven consecutive days .Paw withdrawal me-chanical thresholds ( PWMT) and paw withdrawal thermal latencies ( PWTL) were measured 1 day before STZ adminis-tration, and 3, 7, 10, 14, 21 and 28 days after STZ administration.Meanwhile, the expression of p -STAT3 in DRG was determined by immune-histochemistry .Results Compared with the control , the DNP group presented significantly reduced PWMT (3.8 ±0.84) and PWTL (5.9 ±0.94), and remarkably enhanced expression of p -STAT3 (P<0 .05).Compared with the DNP group, no substantial changes were detected in PWMT (4.03 ±0.5), PWTL (6.2 ±0. 7) and p-STAT3 expression in the SC +DNP group after injection of normal saline (P>0.05).Compared with the DNP and SC+DNP groups, the GBP+DNP group showed higher PWMT (8.4 ±0.87) and PWTL (10 ±1.2), but down-regulated expression of p -STAT3 in DRG (P<0.05).C onclusion Systemic administration of gabapentin can attenuate diabetic neuropatholgical pain by inhibiting the expression of p -STAT3 in DRG.