甘糖酯对糖尿病大鼠视网膜病变中炎性因子TNF-α和IL-1β表达的影响  

Effects of propylene glycol mannite sulfate on the expression of tumor necrosis factor-α and interleukin-1β in the rat with diabetic retinopathy

作　　者：周玮琰[1] 王洪亚[2] 杜秀娟[3] 董卫红[1] 

机构地区：[1]山东大学附属省立医院眼科,中国山东省济南市250021 [2]山东大学附属省立医院检验科,中国山东省济南市250021 [3]山东中医药大学眼科中心山东施尔明眼科医院,中国山东省济南市250002

出　　处：《国际眼科杂志》2016年第8期1444-1448,共5页International Eye Science

基　　金：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)~~

摘　　要：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 m annite sulfate（ PGMS） on the expression of tum or necrosis factor-α（ TNF-α） and interleukin-1β（ IL-1β）,in diabetic retinopathy by a rat m odel, to study the m echanism of PGMS against diabetic retinopathy,and provide a reliable theoretical and experim ental evidence for the PGMS to be applied to clinical prevention and treatm ent of diabetic retinopathy.METHODS： Male Wistar rats were randomized into 4groups,norm al control group, diabetic control group and PGMS in group,the PGMS in groups included the doses of 50 m g / kg and 100 m g / kg. 1% streptozotocin（ STZ） of 60 mg /kg was intraperitoneally injected in ratsto establish the diabetic m odels. The PGMS with the doses of 50 m g / kg and 100 m g / kg were used to gavage in different groups of m odels for 12 wk. Twelve weeks later,the anim als were sacrificed and retinas were isolated.The aqueous hum ors and serum s were taken,expressions of TNF-α and IL-1β protein in retinas,aqueous hum ors and serum s were detected by enzym elinked im m unosorbent assay（ ELISA）,respectively. The location and the expression of TNF-α and IL-1β protein in retina tissue was detected by im m unohistochem istry.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 norm al control group（ P〈0. 05）,but in the groups which PGMS was given reduced, lower than those in diabetes m ellitus（ DM） group,especially as the concentration of PGMS increased（ P〈0. 05）. But the levels of aqueous hum or＇s TNF-α and IL-1β proteins in PGMS group were not reduced. Im m unohistochem istry showed that the TNF-α protein was alm ost not expressed in norm al control group. But the TNF-αprotein was highly expressed in diabetic control group.The expression m ainly located in the ganglion cell layer,the inner plexiform layer, ou

关 键 词：甘糖酯 肿瘤坏死因子-α 白细胞介素-1Β 糖尿病视网膜病变 

分 类 号：R587.2[医药卫生—内分泌]