Effect of angiotensin Ⅱ receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells

细胞外的矩阵蛋白质的减少的降级玩的背景在糖尿病的 nephropathy 的发作的一个重要角色。矩阵 metalloproteinase-9 (MMP-9 ) 是矩阵 metalloproteinase 家庭的成员，和 metalloproteinase-1 (TIMP-1 ) 的织物禁止者与这个过程被联系。血管收缩素 il (AII ) 也在糖尿病的 nephropathy 的发展起一个重要作用。试图在老鼠 mesangial cells.Methods 老鼠 mesangial 房间在 MMP-9 和 TIMP-1 的导致葡萄糖的 mRNA 表情上调查血管收缩素受体 blocker 的效果的这研究进 5 个组有教养、划分：正常葡萄糖(组 NG ) ，高葡萄糖(组 HG ) ，组 NG+AII， NG+AIl+saralasin (组 NG+AII+S， saralasin 是所有受体 blocker ) 并且 HG+saralasin (组 HG+S ) 。在房间被孵化 24 个小时以后，在上层清液的所有集中被放射性免疫测定和 MMP-9 的表示测量， TIMP-1 mRNA 是由反向的抄写聚合酶链反应(RT-PCR ) 的 assayed 所有集中是的 .Results 在组 HG 更高((56.90 慮敳吗？？

Background The decreased degradation of extra-cellular matrix proteins plays an important role in the onset of diabetic nephropathy. Matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1）, which are members of the matrix metalloproteinase family, are associated with this process. Angiotensin Ⅱ （AⅡ） plays an important role in the development of diabetic nephropathy also. This research aimed to investigate the effect of angiotensin Ⅱ receptor blocker on glucose-induced mRNA expressions of MMP-9 and TIMP-1 in rat mesangial cells. Methods Rat mesangial cells were cultured and divided into 5 groups： normal glucose （group NG）, high glucose （group HG）, group NG＋AⅡ, NG＋AⅡ＋saralasin （group NG＋AⅡ＋S, saralasin is the AⅡ receptor blocker） and HG＋saralasin （group HG＋S）. After the cells were incubated for 24 hours, AⅡ concentrations in the supernatant were measured by radioimmunoassay and the expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription-polymerase chain reaction （RT-PCR）. Results AⅡ concentrations were higher in group HG （（56.90±13.54） pg/ml） and group HG＋S （（51.30±5.96） pg/ml） than in group NG （（37.89±8.62） pg/ml, P〈0.05）, whereas there was no significant difference between group HG and group HG＋S. The expression of MMP-9 mRNA and MMP-9/TIMP-1 mRNA ratio in group NG＋AⅡ （MMP-9, 0.33±0.04; MMP-9/TIMP-1, 0.40±0.06） and group HG （MMP-9, 0.36±0.02; MMP-9/TIMP-1, 0.45±0.03） were decreased more significantly than those in group NG （MMP-9, 0.72±0.02; MMP-9/TIMP-1, 1.21±0.07）. These values in group NG＋AⅡ＋S （MMP-9, 0.71±0.02; MMP-9/TIMP-1, 1.18±0.05） were higher than those in group NG＋AⅡ, and the values in group HG＋S （MMP-9, 0.71＋0.02; MMP-9/TIMP-1, 1.16±0.05） were higher than those in group HG （all were P〈0.05）. TIMP-1 mRNA expression was increased more significantly in group NG＋AⅡ （0.81±0.03） and group HG （0.80±0.03） than in group NG （0.59±0.02）, but it was lower in group NG＋AⅡ＋S （0.60±0.01） than in group NG＋AⅡ and also lower in group HG＋S （0.61±0.01） than in group HG （all were P〈0.05）. Conclusions High glucose stimulates AⅡ production. Both high glucose and AⅡ induce a decrease in MMP-9 mRNA expression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA expression, which can be reversed by saralasin, suggesting that high glucose can aggravate impaired matrix degradation by altering gene expression of MMP-9 and TIMP-1 and that the effect of high glucose may be mediated by AⅡ.