甘糖酯对糖尿病大鼠视网膜病变中血管生成因子VEGF表达的影响

doi:10.6040/j.issn.1673-3770.0.2016.146

摘要/Abstract

摘要： 目的探讨甘糖酯对糖尿病大鼠视网膜病变(DR)中血管内皮生长因子(VEGF)表达变化的影响,为将甘糖酯应用于临床上防治DR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,实验对照组,甘糖酯治疗组,其中甘糖酯治疗组分为糖尿病+低甘糖酯组(50 mg/kg甘糖酯)和糖尿病+高甘糖酯组(100 mg/kg甘糖酯)。大鼠采用链脲佐菌素60 mg/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12周。给药12周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VEGF蛋白的表达变化情况,免疫组化检测大鼠视网膜VEGF蛋白表达的变化及表达位置,实时定量PCR检测大鼠视网膜VEGF mRNA表达变化情况。结果给药12周后大鼠DR模型中,甘糖酯对大鼠的血糖没有影响,ELISA检测结果表明,各组大鼠血清中的VEGF蛋白差异没有统计学意义(P>0.05),而糖尿病组大鼠房水及视网膜中的VEGF蛋白含量与正常对照组比较显著增加(P<0.05),甘糖酯干预后房水及视网膜中VEGF蛋白较糖尿病组表达明显降低(P<0.05)。免疫组化检测表明,正常对照组VEGF蛋白呈低表达,糖尿病组VEGF蛋白呈高表达状态,主要在视网膜神经节细胞层、内从状层及外核层高表达;而给予甘糖酯干预后VEGF蛋白呈弱表达。实时定量PCR检测大鼠视网膜中VEGF mRNA,可见正常对照组VEGF mRNA为低表达状态,糖尿病组VEGF mRNA的表达为正常对照组的2.12倍,甘糖酯干预后视网膜VEGF mRNA表达较糖尿病组明显下降(P<0.05)。结论甘糖酯对大鼠早期DR有很好的防治作用,其机制与抑制血管生成因子VEGF的表达与分泌有关。

关键词: 甘糖酯, 血管内皮生长因子, 糖尿病视网膜病变

Abstract: Objective To investigate the influence of propylene glycol mannate sulfate(PGMS)on the expression of vascular endothelial growth factor(VEGF)in diabetic retinopathy(DR)by a rat model, to study the mechanism of PGMS againstDR, and to provide a reliable theoretical and experimental evidence for the PGMs to be applied to clinical prevention and treatment of DR. Methods Male Wistar rats were randomized into the normal control group, the diabetic control group and the PGMS group. The PGMS group was subdivided into the low-dose PGMS group and high-dose PGMS group, with doses of 50 mg/kg and 100 mg/kg, respectively. The 1% Streptozotocin(STZ)of 60 mg/kg was intraperitoneally injected in rats to establish the diabetic models. The PGMS with the doses of 50 mg/kg and 100 mg/kg were used to gavage in different groups of models for 12 weeks. Twelve weeks later, the animals were sacrificed and retinas were isolated. The aqueous humor and serum were taken, expressions of VEGF protein in retina, aqueous humor and serum were detected by ELISA, respectively. The location and the expression of VEGF protein in 山东大学耳鼻喉眼学报31卷2期 -周玮琰,等.甘糖酯对糖尿病大鼠视网膜病变中血管生成因子VEGF表达的影响 \=-retina tissue was detected by immune-histochemistry. Real-time RT-PCR was used to measure the expression of VEGF mRNA in retinas. Results Twelve weeks after the use of PGMS,the level of blood glucose was not changed. ELISA showed that the expression of VEGF protein in serum was not significantly changed in different groups(P>0.05), but the expression of VEGF protein in aqueous humor and retina was significantly increased in diabetic control group than normal control group(P<0.05), but the groups which PGMS was given reduced, lower than that DM group, showing statistically significant differences(P<0.05). Immunohistochemistry showed that the VEGF protein was almost not expressed in normal control group, but the VEGF protein was highly expressed in diabetic control group. The expression mainly located in the ganglion cell layer, the inner plexiform layer, outer nuclear layer. The VEGF protein was weakly expressed at the group of PGMS. Real-time RT-PCR showed the expression of VEGF mRNA was lower in normal control group. The expression of VEGF mRNA in diabetic control group was almost 2.12 times than normal control group. The expression was decreased obviously in the group of PGMS. Conclusion PGMs has a good control effect on early diabetic retinopathy. PGMS can treat the diabetic retinopathy by downregulating the expressions of VEGF in early diabetic retinopathy.

Key words: Diabetic retinopathy, Vascular endothelial growth factor, Propylene glycol mannate sulfate

中图分类号:

R774

周玮琰,王洪亚,杜秀娟,董卫红. 甘糖酯对糖尿病大鼠视网膜病变中血管生成因子VEGF表达的影响[J]. 山东大学耳鼻喉眼学报, 2017, 31(2): 90-95.

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