3-氨基苯甲酰胺抑制糖尿病大鼠晶状体混浊的实验研究

Mechanisms for 3-aminobenzene inhibiting the lens opacity in the streptozotocin-induced diabetic rats: A preliminary study

目的:探讨PARP(聚腺苷二磷酸核糖聚合酶)抑制剂3-氨基苯甲酰胺(3-AB)对糖尿病大鼠晶状体混浊程度的影响及其可能机制。方法:Wistar大鼠随机分为正常对照组、糖尿病组、3-AB干预组。糖尿病组和3-AB干预组大鼠予以腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型,正常对照组注射等体积柠檬酸盐缓冲液。建模成功后3-AB组每日按照30mg/kg给予3-AB灌胃,正常对照组和糖尿病组则给予等体积9g/L生理盐水(NS)灌胃。观察并记录各组大鼠晶状体混浊进展情况,分别于给药后2,4,8wk处死各组大鼠,取出晶状体检测谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)和糖基化终末产物(AGE)的含量,并检测晶状体上皮细胞中基质金属蛋白酶-2(MMP-2)和碱性成纤维细胞生长因子(bFGF)的表达情况。结果:灌胃3wk时糖尿病组和3-AB组大鼠均开始出现不同程度的晶状体混浊,4wk和8wk时糖尿病组晶状体混浊程度比3-AB组重(P<0.01)。3-AB组大鼠晶状体中GSH-Px和SOD活性在2,4,8wk时均高于糖尿病组(均P<0.05),但均低于正常对照组(P<0.01)。3-AB组大鼠晶状体中MDA的含量在2,4,8wk时均低于糖尿病组(P<0.05),但均高于正常对照组(P<0.01)。糖尿病组和3-AB组大鼠晶状体中AGE含量在2,4,8wk时高于正常对照组(均P<0.05),而糖尿病组在2wk和4wk时高于3-AB组(P<0.05),但在8wk时无差异。MMP-2在正常对照组大鼠晶状体上皮细胞几乎无表达,在2,4,8wk时糖尿病组均强于3-AB组(P<0.05)。bFGF在三组大鼠晶状体上皮细胞均呈阳性表达;在2,4,8wk时,糖尿病组和3-AB组均强于正常对照组(均P<0.05),但糖尿病组与3-AB组之间无差异。结论:3-AB对STZ诱导的糖尿病大鼠晶状体混浊具有一定抑制作用,其机制可能是通过减轻STZ诱导的糖尿病大鼠晶状体上皮细胞氧化损伤,降低非酶糖基化水平,抑制晶状体上皮细胞中MMP-2的表达,减轻晶状体上皮细胞外基质降解,从而抑制晶状体混浊。

AIM ： To investigate the effect and possible mechanism of poly ADP-ribose polymerase （PARP） inhibitor 3- aminobenzene （3-AB） on the lens opacity in the diabetic rats. METHODS： Wistar rats were randomly divided into three groups： control group, diabetic group and 3-AB group. The rats of diabetic group and 3-AB group were treated with intraperitoneal injection of streptozotocin （STZ）. The rats of control group were given the same volume of citrate buffer. After the model constructed, 3- AB group was treated with 3-AB （30 mg/kg） gavage daily while the control group and diabetic group were given the same volume of 0.9% NS instead. The progress of lens opacity of rats was observed and recorded. After administrated for 2, 4 and 8 weeks, rats were sacrificed and taken lens respectively. The lens were used to detected the activity of glutathione peroxidase （GSH-px）, superoxide dismutase （SOD）, the level of malondialdehyde （MDA） and advanced glycation end products CAGE）, the expression of matrix metalloproteinase- 2 （ MMP- 2） and basic fibroblast growth factor （bFGF） in lens epithelial cells. RESULTS： Lens of diabetic group and 3- AB group appeared various degree of cloudy since the third week. The level of diabetic group was higher than 3-AB group （ P〈0.01 ） in the fourth and eighth week. The GSH-Px and SOD activities of diabetic group were lower than 3-AB group （all P〈0.05） at the 2, 4, 8 weeks, but all of them lower than control group （P〈0.01）. The content of MDAincreased in diabetic group and 3-AB group, compared with control group （ P〈0.01 ）, and its content in diabetic group was higher than in 3-AB group （P〈0.05） at the 2, 4, 8 weeks. The content of AGE in the lens that come from control group were lower than diabetic group and 3- AB group （all P〈0.05） in each time. At 2, 4 weeks, its content in diabetic group was higher than in 3-AB group （P〈0.05）, but there was no difference at 8 weeks （P〉 0.05）. There was rare expression of MMP-2 in control group, the MMP- 2 expression of diabetic group is statistically significant higher than 3-AB group （P〈0.05） in the 2, 4, 8 weeks, bFGF was expressed in the three groups, and the bFGF expression of control group was lower than diabetic group and 3-AB group （all P〈0.05） in the 2, 4, 8 weeks. There was no difference between diabetic group and 3-AB group in each time. CONCLUSION： 3-AB has a certain inhibitory effect for lens opacity in the S＇l-Z-induced diabetic rats, the possible mechanism：alleviates the oxidative damage of lens epithelial cells, reduces the level of non-enzyme glycation, and inhibits the expression of MMP-2 suggested that it can alleviate the degradation of lens epithelial cells＇ extracellular matrix, which lead to inhibit the lens opacity.