Background The decreased degradation of extra-cellular matrix proteins plays an important role in the onset ofdiabetic nephropathy.Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1),which aremembers of the matrix metalloproteinase family,are associated with this process.Angiotensin Ⅱ(All) plays an importantrole in the development of diabetic nephropathy also.This research aimed to investigate the effect of angiotensin Ⅱreceptor 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 (groupHG),group NG+All,NG+All+saralasin (group NG+All+S,saralasin is the All receptor blocker) and HG+saralasin (groupHG+S).After the cells were incubated for 24 hours,All concentrations in the supernatant were measured byradioimmunoassay and the expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription-polymerasechain reaction (RT-PCR).Results All concentrations were higher in group HG ((56.90±13.54) pg/ml) and group HG+S ((51.30±5.96) pg/ml) thanin group NG ((37.89±8.62) pg/ml,P<0.05),whereas there was no significant difference between group HG and groupHG+S.The expression of MMP-9 mRNA and MMP-9/TIMP-1 mRNA ratio in group NG+All(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 moresignificantly than those in group NG (MMP-9,0.72±0.02;MMP-9/TIMP-1,1.21±0.07).These values in group NG+All+S(MMP-9,0.71±0.02;MMP-9/TIMP-1,1.18±0.05) were higher than those in group NG+All,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 mRNAexpression was increased more significantly in group NG+All(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+All+S (0.60±0.01) than in group NG+All and also lower in group HG+S(0.61±0.01) than in group HG (all were P<0.05).Conclusions High glucose stimulates All production.Both high glucose and All induce a decrease in MMP-9 mRNAexpression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA expression,which can be reversedby saralasin,suggesting that high glucose can aggravate impaired matrix degradation by altering gene expression ofMMP-9 and TIMP-1 and that the effect of high glucose may be mediated by All. 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- are associated with this process. Angiotensin Ⅱ (All) plays an importantrole in the development of diabetic nephropathy also. This research aims 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 (groupHG), group NG + All, NG + All + saralasin (group NG + All + S, saralasin is the All receptor blocker) and HG + saralasin (groupHG + S). After the cells were incubated for 24 hours, the concentrations of the supernatant were measured by radioimmunoassay and the expression of MMP-9 and TIMP- 1 mRNA was assayed by reverse transcription-polymerasechase Results of the in-group HG ((56.90 ± 13.54) pg / ml) and group HG + S ((51.30 ± 5.96) pg / ml) groups in in group NG ((37.89 ± 8.62) pG / ml, P <0.05), there was no significant difference between group HG and groupHG + S.The expression of MMP-9 mRNA and MMP-9 / TIMP- 0.33 ± 0.04; MMP-9 / TIMP-1 .40 ± 0.06) and group HG (MMP-9, 0.36 ± 0.02; MMP- 9 / -TIMP- 1, 10.4 ± 0.03) were decreased more than statistically more than those in group NG ( These values ​​in group NG + All + S (MMP-9, 0.71 ± 0.02; MMP-9 / TIMP- 1, 1.18 ± 0.05 ) were higher than those in group NG + All, 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 TMP-1 mRNA expression was increased more significantly in group NG + All (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 + All + S (0.60 ± 0.01) than in group NG + All and lower lower group group HG + S (0.61 0.01) than in groupHG (all were P <0.05) .Conclusions High glucose stimulates All production. Both high glucose and All 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 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 All.