罗格列酮对高糖培养的大鼠系膜细胞增生及p27表达的影响

目的:探讨罗格列酮对糖尿病肾病保护作用的机制。方法:体外培养的大鼠系膜细胞分为正常对照组(NG,含5.6mmol/L D-葡萄糖),NG+甘露醇(25 mmol/L)组,高糖组(HG,含30mmol/L D-葡萄糖),HG+罗格列酮(5μmol/L)组,HG+罗格列酮(10μmol/L)组,HG+罗格列酮(20μmol/L)组。用MTT法测定细胞增生,免疫细胞化学法测定p27Kip1表达。结果:(1)培养72小时后,在模拟高血糖的高糖培养基中,各浓度罗格列酮均可抑制大鼠系膜细胞增生,且此作用与渗透压改变无关。(2)与NG组相比,HG组培养24小时p27表达降低(P<0.05),与其增生活跃相一致,随时间延长,p27表达量逐渐增加,48、72小时无明显差异。与HG组相比,5μmol/L罗格列酮组作用24、48小时无明显差异,作用72小时p27表达增加(P<0.05);10μmol/L、20μmol/L罗格列酮组在各时间点均增加p27表达,有统计学意义。随着罗格列酮剂量增加,p27表达也明显增加。结论:在高糖环境下罗格列酮至少部分通过增加p27表达引起系膜细胞增生抑制,从而对糖尿病肾病起保护作用。

Rosiglitazone inhibits rat mesangial cell proliferation exposed to high glucose and increasesexpression of p27Kip1 protein

Objective: To investigate the effects of rosiglitazone on cell proliferation and expression of p27Kip1 protein in mesangial cells.Methods:Rat mesangial cells were cultured in vitro,and were divided into six groups : normal glucose group(NG,5.6mmol/L D-glucose),NG + mannitol(25 mmol/L),high glucose group(HG,30mmol/L D-glucose),HG+ RGZ(5μmol/ L),HG+ RGZ(10μmol/ L) and HG+ RGZ(20μmol/ L).Rosiglitazone-treated rat mesangial cells exposed to high glucose were analyzed for cell proliferation by use of MTT assay.Cell cycle-dependent kinase inhibitor p27Kip1 was detected by use of immunocytochemistry assay.Results:(1)After 72 hours,Rosiglitazone-treated rat mesangial cell proliferation in media containing high glucose(30mmol/L) to mimic hyperglycemia assessed by MTT assay,was significantly decreased.Compared with NG,treatment of rat mesangial cells with mannitol,to control for possible nonspecific effects of changes in osomolarity on rat mesangial cell proliferation,had no statistically significance.(2)In contrast to normal glucose,high glucose increased protein synthesis of p27Kip1.Compared with high glucose,rosiglitazone treatment appeared to increase p27 expression in a dose-dependent and time-dependent manner.Conclusions:Rosiglitazone was effective for suppression of rat mesangial cell proliferation exposed to high glucose,partly by increasing synthesis of p27Kip1.