丙酮酸对糖尿病大鼠晶状体多元醇通路及上皮细胞凋亡的影响  

Effect of pyruvate on polyol pathway and lens epithelium apoptosis in diabetic rats

作　　者：齐艳秀[1,2] 于海莲[3] 孟德欣[4] 张涤[3] 张劲松[1] 

机构地区：[1]中国医科大学附属第四医院眼科,沈阳110001 [2]佳木斯大学附属第一医院 [3]佳木斯大学附属第一医院眼科 [4]佳木斯大学基础医学院生理教研室

出　　处：《中华眼科杂志》2007年第12期1119-1124,共6页Chinese Journal of Ophthalmology

摘　　要：目的探讨在糖尿病性白内障形成中多元醇通路活性增强对晶状体上皮细胞凋亡和caspase-3活性的影响，以及丙酮酸的对抗作用。方法将Wistar大鼠220只随机分成3组：对照组（60只），模型组（80只），治疗组（80只）。模型组、治疗组应用链脲佐菌素（STZ）诱发糖尿病，治疗组饲料及饮水中添加2％丙酮酸钠。每2周用手持式裂隙灯显微镜观察晶状体的改变，分别于实验4、8和12周采用高效液相色谱仪检测3组大鼠晶状体组织中葡萄糖、山梨醇含量变化，流式细胞术检测晶状体上皮细胞凋亡，免疫印迹法分析caspase-3的活化。结果12周后模型组晶状体全部有不同程度的白内障形成，而在同一时间段治疗组晶状体的混浊程度明显轻于模型组。模型组与对照组比较，大鼠晶状体组织中葡萄糖、山梨醇含量显著升高，细胞凋亡率上升，并伴随caspase-3活化增高。治疗组与模型组比较，晶状体组织中葡萄糖、山梨醇含量显著降低，细胞凋亡率下降，caspase-3活化降低。结论多元醇通路代谢增强是糖尿病大鼠晶状体上皮细胞凋亡的重要诱发因素，可能通过活化caspase-3途径而诱导晶状体上皮细胞凋亡。丙酮酸可通过抑制多元醇代谢通路的活性增强而有效的抑制晶状体上皮细胞的凋亡，延缓糖尿病性白内障的形成。Objective To investigate the effect of polyol pathway on the lens epithelium apoptosis and caspase-3 activity and its reversal by pyruvate in diabetic rats. Methods Two hundred and twenty Wistar rats were divided into 3 groups： control group （60 rats）, experiment group （80 rats） and treatment group （ 80 rats）. After streptozotocin （ STZ ） induced cataract, the treatment group received 2% pyruvate in the diet and drinking. Lens opacification was detected by microscope every 2 weeks. Amounts of glucose and sorbitol in the lens were quantified by high-performance liquid chromatography 4, 8 and 12 weeks after the treatment. The percentage of lens epithelium undergoing apoptosis was measured by Annexin V-PI staining. The activity of caspase-3 was analyzed by Western-blot. Results Present study showed that there was significant increase of glucose and sorbitol in the lens in the experiment group, the apoptosis rate and caspase-3 activity of lens epithelium were also gradually increased. Pyruvate treatment decreased the levels of sorbitol, glucose, lens epithelium apoptosis and caspase-3 activity. The progress of cataract was also significantly delayed. Conclusions Activation of polyol pathway, possibly through regulation of the activity of caspase-3, can induce apoptosis of the lens epithelium. Pyruvate ingested orally can effectively inhibit diabetic cataractogenesis in rats through inhibit polyol pathway.

关 键 词：糖尿病 实验性 晶体 上皮细胞 山梨醇 细胞凋亡 半胱氨酸天冬氨酸蛋白酶 丙酮酸 

分 类 号：R686[医药卫生—骨科学]