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[摘要]
目的:观察N-乙酰半胱氨酸与曲尼司特联合使用对糖尿病大鼠视网膜相关检测指标的影响,评估其对血管内皮细胞和周细胞的保护作用。 方法: 用链脲佐菌素建立糖尿病大鼠模型60只,分为曲尼司特(TNL)组、N-乙酰半胱氨酸(NAC)组、联合用药(COM)组、模型(DM)组和空白对照(NOR)组。常规饲养12wk测定大鼠血清GSH-Px与SOD,免疫组织化学检测视网膜TNF-α和NF-κB的表达,观察视网膜血管消化铺片形态,并行血管内皮细胞与周细胞计数。 结果:与正常组相比,糖尿病模型各组GSH-Px与SOD均不同程度降低,其中DM与TNL组较NAC组和COM组降低显著。TNF-α与NF-κB在DM组表达均为最高,NOR最低,其余三组均不同程度降低,以COM组降低为著(P<001)。血管铺片示DM组血管形态以及周细胞与内皮细胞的损害明显,用药后有改善,以COM组为著。 结论:NAC与TNL联合使用对DR血管内皮细胞与周细胞的损害有明显治疗作用,其作用机制可能与拮抗自由基、炎症反应以及抑制肥大细胞释放细胞因子有关。
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[Abstract]
AIM:To investigate the change of the endothelial and perivascular cell in an model of diabetic retinopathy (DR), correlate retinal and plasma results and to evaluate the influence of treatment by N-acetylcysteine (NAC) and Tranilast(TNL). METHODS: Five groups were studied: control (Group NOR), streptozotocin (STZ)-induced diabetic rats (Group DM), STZ rats following 12 weeks of NAC (Group NAC), TNL(Group TNL) and both NAC and TNL(Group COM). Plasma levels of superoxide dismutase (SOD) and glutathione(GSH) were obtained. Primary antibodies against tumour necrosis factor-alpha(TNF-α),nuclear factor κB(NF-κB) were used.The retinal vasculature isolated by using the trypsin digest method was observed. RESULTS: Plasma levels of SOD and GSH were lower in Group DM and TNL than the others. Expression of TNF-α was robust in Group DM, mild in Group COM,TNL and NAC, weak in Group NOR. Intensity of NF-κB was higher in Group DM,TNL and NAC compared with Group NOR and COM. The vascular structures of Group COM were much improved than other STZ models. CONCLUSION: Pericyte loss and endothelial cell hyperplasia occur early in DR. These changes are associated with oxidative stress and inflammation and could be minimized by treatment with NAC and TNL. The results suggest that the therapy worked through reducing ROS and inhibiting degranulation of mast cell. This treatment could neutralize the events in diabetic retinopathy in STZ model.
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