盐酸度洛西汀对糖尿病神经病理痛大鼠脊髓背角星形胶质细胞和小胶质细胞的影响

摘要

目的：观察盐酸度洛西汀对糖尿病神经病理痛大鼠脊髓背角星形胶质细胞和小胶质细胞的影响。方法将30只SD大鼠随机分为3组：对照组（Control组），模型组（DNP组），盐酸度洛西汀组（DLX组）各10只。链脲佐菌素（STZ）注射前1 d及注射后7，14，21，28 d测定大鼠机械缩足阈值（MWT）和热缩足潜伏期（TWL）。DLX组于STZ注射15 d起腹腔注射10 mg/kg盐酸度洛西汀，连续14 d，并于14，21，28 d测定WMT和TWL。行为学检测完成后选择28 d大鼠用免疫荧光法、蛋白印迹法测定脊髓背角GFAP、iba-1的表达。结果造模前大鼠MWT、TWL无明显差异（P>0.05）。造模后DNP组、DLX组较Control组MWT降低、TWL缩短（P<0.05），且GFAP与iba-1的表达较Control组上调（P<0.05）；腹腔注射度洛西汀后，与DNP组比较，DLX组MWT升高，TWL延长，且GFAP与iba-1表达下调（P<0.05）。结论盐酸度洛西汀能明显减轻糖尿病大鼠神经病理性疼痛，其机制可能与抑制星形胶质细胞和小胶质细胞的表达有关。%ObjectiveTo investigate the effect of duloxetine on diabetic neuropathic pain(DNP)and expression of astrocytes and microglia in spinal dorsal horn in rats.MethodsThirty male SD rats were randomly divided into 3 groups:control group(group C),DNP group(group DNP),duloxetine group(group DLX)(n=10 each).Diabetes was induced with streptozocin(65mg/kg)subcutaneously.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency (TWL)were measured at 1 d before and 7,14,21,28 d after streptozocin injection.Duloxetine was given intraperitoneally once a day for 14 days starting from 15 d after streptozocin injection in DLX group respectively.The expression of GFAP and iba-1 was determined at 28d after streptozocin injection by Immunofluorescence and western blot.ResultsThere was no significant difference in MWT and TWL before streptozocin injection(P>0.05).Compared with group C,MWT was significantly decreased and TWL was significantly shortened in DNP,DLX groups(P<0.05).Compared with group C,the expression of GFAP and iba-1 was up-regulated in group DLX(P<0.05).Compared with group DNP,MWT was significantly increased,TWL was significantly prolonged and the expression of GFAP and iba-1 in spinal dorsal horn was down-regulated in DLX group(P<0.05).Conclusionduloxetine can alleviate diabetic neuropathic pain through inhibition of the expression of GFAP and iba-1 in spinal dorsal horn.