目的 探讨舒洛地特对大鼠糖尿病视网膜病变的修复及MAPK通路的调节作用。   方法 72只大鼠随机分为正常对照组、糖尿病视网膜病变组、舒洛地特低、中、高剂量组及盐酸二甲双胍组，12只/组；除正常对照组外，其余大鼠均腹腔注射链脲佐菌素建立糖尿病视网膜病变大鼠模型；舒洛地特低、中、高剂量组分别灌胃给予 10 mg/kg、 20 mg/kg、40 mg/kg舒洛地特，盐酸二甲双胍组给予200 mg/kg盐酸二甲双胍，1次/d，给药12周。检测大鼠空腹血糖(FBG)、糖化血红蛋白(HbA1c)水平，以及血清晚期糖基化终末产物(AGEs)、白细胞介素6(IL-6)、IL-1β 水平，以及视网膜组织葡萄糖转运蛋白1(GLUT-1)、葡萄糖转运蛋白3(GLUT-3)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平；Western blotting及免疫组织化学检查视网膜p38 MAPK、磷酸化p38 MAPK（p-p38 MAPK）水平；HE染色法检查视网膜病理学变化及神经节细胞计数。   结果 与糖尿病视网膜病变组比较，舒洛地特各剂量组大鼠FBG及HbA1c水平、血清AGEs、IL-6、IL-1β水平、视网膜组织GLUT-1、GLUT-3、MDA水平，p38 MAPK、p-p38 MAPK/p38 MAPK水平及免疫组织化学积分吸光度均显著降低(P<0.05)，视网膜组织SOD水平及神经节细胞数均显著升高(P<0.05)。   结论 舒洛地特能够调节糖尿病视网膜病变大鼠血糖水平及视网膜组织糖代谢，修复视网膜病理损伤，其机制可能与调节MAPK通路有关。

Objective  To study the effect of sulodexide on the repair of diabetic retinopathy and the regulation of MAPK pathway in rats.    Methods  Totally 72 rats were randomly divided into normal control group, diabetic retinopathy group, low, middle and high dose of sulodexide group and metformin hydrochloride group. Except normal control group, other rats were intraperitoneally injected with streptozotocin to establish the rat model of diabetic retinopathy. Rats in the low, middle and high dose sulodexide groups were given sulodexide by intragastric administration of 10 mg/kg，20 mg/kg and 40 mg/kg, respectively. Metformin hydrochloride group was given metformin hydrochloride of 200 mg/kg, once a day for 12 weeks. The levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and serum levels of advanced glycation end products (AGEs), interleukin-6 (IL-6), IL-1β, and levels of glucose transporter 1 (GLUT-1), glucose transporter 3(GLUT-3), superoxide dismutase (SOD) and malondialdehyde (MDA) in retina were detected. The levels of p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) in retina were detected by immunohistochemistry and Western blotting. Retinal pathological changes and ganglion cell count were examined by HE staining.    Results The levels of FBG and HbA1c, serum AGEs, IL-6, IL-1 β, GLUT-1, GLUT-3, MDA and p38 MAPK mRNA, p38 MAPK, p-p38 MAPK/p38 MAPK and immunohistochemical integral optical density of retina in sulodexide group were significantly lower than those in diabetic retinopathy group (P<0.05), while the SOD level and ganglion cell number in retinal tissue were significantly higher than those in diabetic retinopathy group (P<0.05).    Conclusion  Sulodexide can regulate blood glucose level and retinal glucose metabolism in diabetic retinopathy rats, and repair retinal pathological damage, and its mechanism may be related to the regulation of MAPK pathway.