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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

引用

Chinese Medical Journal 2007年第21期120卷 1886-1889页

作者： DING He-lin GUO Ying XU Ming-tong LI Hai-yan FU Zu-zhi Department of Endocrinology Second Affiliated Hospital of Sun Yat-Sen University Guangzhou 510120 China

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

关键词： matrix metalloproteinase-9 tissue inhibitor of metalloproteinase-1, high glucose angiotensin Ⅱ

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