恒定和波动高糖对大鼠肾系膜细胞损伤及RAGE表达的影响

Damage to the cultured rat mesangial cells by constant and intermittent high glucose

目的 研究恒定和波动高糖对大鼠肾小球系膜细胞（GMC）损伤及细胞晚期糖基化终末产物受体（RAGE）表达的影响,探讨糖尿病肾病的病理损伤机制.方法 将体外培养的大鼠GMC在恒定和波动高糖培养基中培养,分别于24 h、48 h进行细胞学形态观察,四甲基偶氮唑蓝（MTT）法测定细胞存活率,生化法测定培养上清液中超氧化物歧化酶（SOD）活性和丙二醛的含量,RT-PCR检测细胞RAGE mRNA的表达情况.结果 波动高糖组在细胞形态、SOD活性、丙二醛含量、RAGE mRNA的表达与正常对照组和恒定高糖组相比均有明显差异（P＜0.05）.结论 波动高糖造成大鼠GMC损伤比恒定高糖更为严重,是导致糖尿病肾病发生的重要原因之一.

Objective To study the impairment and the expression of receptor of advanced glycation endproduct （RAGE） in cultured rat glomerular mesangial cells （ GMC ） induced by constant and intermittent high glucose, and to investigate the pathogenesis of diabetic nephropathy. Methods After being cultured under constant and intermittent high glucose with different concentrations for 24 and 48 hours, the morphological changes of rat mesangial cells were observed, the proliferation of GMC was detected by MTT assay, the activity of superoxide dismutase （SOD）and the level of malondialdehyde （MDA）in supernatant were measured by spectrophotometer,and the expressions of RAGE mRNA were evaluated by RT-PCR. Results （ 1 ） Compared with the control group,the cellular morphology was changed in case of constant and intermittent high glucose. The damage of GMC with intermittent high glucose concentrations was more serious. （2）The activity of SOD was decreased and the level of MDA was raised in case of intermittent high glucose concentrations compared with the constant high glucose concentrations （P〈0.05）. （3）The expression of RAGE mRNA with intermittent high glucose concentrations was significantly higher than that with constant high glucose concentrations （ P〈0. 01 ）. Conclusions The damaging effects and increased expression of RAGE in cultured rat GMC induced by blood glucose fluctuation was much worse than that with constant high glucose. The blood glucose fluctuation may be one of the causes that induce diabetic nephropathy.