目的：探讨甘糖酯对糖尿病大鼠视网膜病变中炎性因子肿瘤坏死因子-α(tumor necrosis factor，TNF-α)和白细胞介素-1β(interleukin-1β，IL-1β)表达变化的影响，为将甘糖酯应用于临床上防治糖尿病视网膜病变提供可靠的理论和实验依据。

方法：选取清洁级雄性成年Wistar大鼠，随机分为正常对照组、糖尿病组、50mg/kg甘糖酯治疗组和100mg/kg甘糖酯治疗组。大鼠采用链脲佐菌素(STZ)60mg/kg一次性腹腔内注射制作糖尿病模型，甘糖酯治疗组的给药方法为甘糖酯溶液灌胃，持续12wk。给药12wk后处死各组大鼠并分离视网膜，取房水、血清，用ELISA法检测大鼠视网膜组织、房水及血清中TNF-α和IL-1β蛋白的表达变化，免疫组织化学检测大鼠视网膜TNF-α和IL-1β蛋白表达的变化。

结果：给药12wk后大鼠糖尿病视网膜病变模型中，甘糖酯对糖尿病大鼠的血糖没有影响； ELISA检测表明，糖尿病组大鼠血清与视网膜中的TNF-α和IL-1β含量增加，与正常对照组比较，差异有统计学意义(P<0.05)； 甘糖酯干预后血清及视网膜中TNF-α和IL-1β显著降低，与糖尿病组比较差异有统计学意义(P<0.05)，且甘糖酯浓度越高，降低越明显。但是甘糖酯干预组房水中TNF-α和IL-1β蛋白的产生无明显变化。免疫组织化学检测表明，正常对照组视网膜中几乎不表达TNF-α蛋白，糖尿病组TNF-α蛋白呈高表达状态，主要位于视网膜神经节细胞层内丛状层、外丛状层及色素上皮层； 50mg/kg甘糖酯干预组TNF-α弱表达，100mg/kg甘糖酯干预组TNF-α几乎不表达。而在正常对照组视网膜中IL-1β在外核层微量表达，糖尿病组IL-1β在内丛状层、外丛状层及色素上皮层高表达； 50mg/kg甘糖酯干预组及100mg/kg甘糖酯干预组IL-1β呈低表达。

结论：甘糖酯能抑制大鼠早期糖尿病视网膜病变中的炎性因子TNF-α和IL-1β的产生，提示其可能对糖尿病视网膜病变起着防治作用。

AIM: To investigate the influence of propylene glycol mannite sulfate(PGMS)on the expression of tumor necrosis factor -α(TNF-α)and interleukin-1β(IL-1β), in diabetic retinopathy by a rat model, to study the mechanism of PGMS against diabetic retinopathy, and provide a reliable theoretical and experimental evidence for the PGMS to be applied to clinical prevention and treatment of diabetic retinopathy.

METHODS: Male Wistar rats were randomized into 4 groups, normal control group, diabetic control group and PGMS in group, the PGMS in groups included the doses of 50mg/kg and 100mg/kg. 1% streptozotocin(STZ)of 60 mg/kg was intraperitoneally injected in rats to establish the diabetic models. The PGMS with the doses of 50mg/kg and 100mg/kg were used to gavage in different groups of models for 12wk. Twelve weeks later, the animals were sacrificed and retinas were isolated. The aqueous humors and serums were taken, expressions of TNF-α and IL-1β protein in retinas, aqueous humors and serums were detected by enzyme-linked immunosorbent assay(ELISA), respectively. The location and the expression of TNF-α and IL-1β protein in retina tissue was detected by immunohistochemistry.

RESULTS: Twelve weeks after the use of PGMS, the level of blood glucose was not changed. ELISA showed that the expression of TNF-α and IL-1β protein in serum and retina was significantly increased in diabetic control group than in normal control group(P<0.05), but in the groups which PGMS was given reduced, lower than those in diabetes mellitus(DM)group, especially as the concentration of PGMS increased(P<0.05). But the levels of aqueous humor's TNF-α and IL-1β proteins in PGMS group were not reduced. Immunohistochemistry showed that the TNF-α protein was almost not expressed in normal control group. But the TNF-α protein was highly expressed in diabetic control group. The expression mainly located in the ganglion cell layer, the inner plexiform layer, outer plexiform layer and pigment epithelium. The TNF-α protein was weakly expressed at the group of 50mg/kg PGMS, the TNF-α protein was almost not expressed at the group of 100mg/kg PGMS. When the normal control group was detected, the IL-1β protein was weakly expressed in the outer plexiform layer. But the IL-1β protein was also highly expressed in diabetic control group.The expression mainly located in the inner plexiform layer, outer plexiform layer and pigment epithelium. The IL-1β protein was weakly expressed at the group of 50mg/kg and 100mg/kg PGMS.

CONCLUSION: PGMS can treat the diabetic retinopathy by downregulating the expressions of TNF-α and IL-1β in early diabetic retinopathy. PGMS maybe have a good control effect on early diabetic retinopathy.

山东省科学技术发展计划(No.2010G0020239); 山东省优秀中青年科学家科研奖励基金(No.BS2014YY060)