白藜芦醇抑制系膜细胞增殖治疗糖尿病大鼠早期肾损害的研究

Treatment research on early diabetic nephropathy rats by resveratrol inhibiting mesangial cell

目的探讨白藜芦醇对糖尿病大鼠早期肾脏损害的保护作用及对系膜细胞增殖的影响,为白藜芦醇治疗糖尿病肾病(DN)提供实验依据。方法建立糖尿病雄性Wistar大鼠模型,成模后随机分为糖尿病组(8只)和白藜芦醇组(8只,予白藜芦醇干预),另设对照组(8只)。观察8周,比较各组空腹血糖、肌酐、肾质量/体质量、24 h尿蛋白定量及肾脏病理学改变。体外培养大鼠系膜细胞并将其分为5组,包括对照组、晚期糖基化终末产物(AGE)组、白藜芦醇2.5、5、10组(在AGE组的基础上加予白藜芦醇干预,终浓度分别为2.5、5、10μmol/L),比较5组细胞增殖率、细胞周期及细胞凋亡率。结果实验第8周末,糖尿病组空腹血糖、肌酐、肾质量/体质量、24h尿蛋白定量高于对照组(P<0.01);白藜芦醇组空腹血糖、肌酐、肾质量/体质量、24 h尿蛋白定量低于糖尿病组(P<0.05);白藜芦醇组肾脏病理改变较糖尿病组轻。AGE组细胞增殖率较对照组高(P<0.01);白藜芦醇各组增殖率均较AGE组低(P<0.01)。AGE组G1期细胞比例较对照组高(P<0.05);白藜芦醇组G1期细胞比例较AGE组少,其中白藜芦醇5、10组与AGE组比较差异有统计学意义(P<0.05、P<0.01)。AGE组S期细胞比例较对照组少(P<0.05);白藜芦醇组S期细胞比例较AGE组高,其中白藜芦醇5、10组与AGE组比较差异有统计学意义(P<0.05、P<0.01)。白藜芦醇5、10组细胞凋亡率较AGE组高(P<0.05、P<0.01)。结论白藜芦醇能改善糖尿病大鼠早期肾脏损害,其机制可能与影响细胞周期、抑制系膜细胞增殖有关。

Objective To investigate the potential renoprotective effect of resveratrol （RSV）on dia-betic nephropathy and mesangial cell,to provide experimental evidence for treatment of resveratrol on diabetic nephropathy. Methods Male diabetic Wistar rats were injected with to induce diabetic rats,and were ran-domly divided into diabetic group （DM group,n=8）and RSV treated group （RSV group,n=8）. The nor-mal Wistar rats were enrolled as control group （C group,n =8）. After 8 weeks,fasting plasma glucose （FPG）,serum creatinine （SCr）,Kidney weight/body weight （Kw/Bw）,24 h amount of urine protein and the pathologic changes of renal tissue were compared in three groups. Cultured rat mesangial cells （RMC）were exposed to advaneed glyeation endproduets （AGE）in the absence and presence of indicated concentrations of resveratrol （2.5,5.0 and 1 0.0 μmol/L）and were divided into control group （C group）,AGE group,RSV 2.5 ,5.0 and 1 0.0 groups. Proliferation,cell cycle and apoptosis of RMC were analyzed. Results After 8 weeks,the levels of FPG,SCr,Kw/Bw,24 h amount of urine protein of DMgroup were higher than those of C group （P〈0.01 ）. The levels of FPG,SCr,Kw/Bw and 24 h amount of urine protein of RSV group were lower than those of DM group （P〈0.05 ,P〈0.01 ）. The pathologic changes were ameliorated in RSV group. Pro-liferation in AGE group was significantly higher compared to C group （P〈0.01 ）. Proliferation of all RSV＆amp;nbsp;groups were lower compared to AGE group （P〈0.01 ）. The percent of G1 in AGE group increased relative to C group （P〈0.05 ）. The percent of G1 in RSV5 and RSV1 0 groups decreased compared to AGE group （P〈0.05 ,P〈0.01 ）. The percent of S in AGE group reduced compared to C group （P〈0.05 ）. The percent of S in RSV5 and RSV1 0 groups increased compared to AGE group （P〈0.05 ,P〈0.01 ）. The percent of apopto-sis in RSV5 and RSV1 0 groups were higher compared to AGE group （P〈0.05 ,P〈0.01 ）. Conclusion Resveratrol can improve early renal damage in diabetic rats,the mechanism may be related to inhibiting me-sangial cell proliferation.