Wan Xia, Huang Hu-hui, Li Jing-gao
Department of Nephrology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Di Yi Jun Yi Da Xue Xue Bao. 2004 Dec;24(12):1391-4.
To investigate the changes of the mRNA expressions of membrane type 3-matrix metalloproteinase (MT3-MMP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2) in diabetic rat kidneys and the effect of losartan on such changes.
Three groups of male Wistar rats were used in this study, namely group A as the control group (n=11), group B consisting of diabetic rats without any therapy (n=11), and group C treated with losartan (n=9). Six months after treatment, the kidneys were taken from the rats to measure the mRNA expressions of MT3-MMP, TIMP2 and transforming growth factor beta1eTGFbeta1 with reverse transcriptional PCR (RT-PCR), and observe the glomerular basement membrane thickening and mesangial matrix MMedensity (MM area/mesangial area) with electron microscope. Twenty-four-hour urine was also collected to measure urinary albumin excretion (UAE).
The expression of renal MT3-MMP mRNA in group B (1.37+/-0.96) was significantly stronger than those in group A (0.75+/-0.34, P<0.05) and in group C (0.75+/-0.30, P<0.05). The mRNA expression of renal TIMP2 in group B (0.73+/-0.37) was significantly increased as compared with group A (0.32+/-0.19, P<0.05) and group C (0.34+/-0.17, P<0.05), with a higher mRNA expression of renal TGFbeta1 in group B (0.53+/-0.20 vs 0.26+/-0.13 in group A and 0.29+/-0.15 in group C, P<0.05). UAE in group B (2.18+/-1.98 mg) was significantly higher than those in groups A and C (0.41+/-0.47 mg/d, P<0.05; 0.65+/-0.89 mg/d, P<0.05, respectively). The glomerular basement membrane thickness (532+/-108 nm) and the MM density (56.4+/-6.8) were significantly greater in group Bthan in the other two groups (P<0.05).
MT3-MMP and the TIMP2 mRNA expressions are significantly increased in diabetic rat kidneys. Losartan can prevent the development of diabetic nephropathy and inhibit MT3-MMP and the TIMP2 mRNA expressions in diabetic rat kidneys.
探讨糖尿病大鼠肾脏中膜型3 - 基质金属蛋白酶（MT3 - MMP）和基质金属蛋白酶组织抑制剂2（TIMP2）mRNA表达的变化以及氯沙坦对此类变化的影响。
本研究采用三组雄性Wistar大鼠，即A组作为对照组（n = 11），B组为未接受任何治疗的糖尿病大鼠（n = 11），C组用氯沙坦治疗（n = 9）。治疗6个月后，取大鼠肾脏，用逆转录聚合酶链反应（RT - PCR）检测MT3 - MMP、TIMP2和转化生长因子β1（TGFβ1）的mRNA表达，并用电子显微镜观察肾小球基底膜增厚和系膜基质密度（系膜面积/系膜区面积）。同时收集24小时尿液检测尿白蛋白排泄率（UAE）。
B组肾MT3 - MMP mRNA表达（1.37±0.96）显著强于A组（0.75±0.34，P < 0.05）和C组（0.75±0.30，P < 0.05）。B组肾TIMP2的mRNA表达（0.73±0.37）与A组（0.32±0.19，P < 0.05）和C组（0.34±0.17，P < 0.05）相比显著增加，B组肾TGFβ1的mRNA表达更高（0.53±0.20，A组为0.26±0.13，C组为0.29±0.15，P < 0.05）。B组UAE（2.18±1.98 mg）显著高于A组和C组（分别为0.41±0.47 mg/d，P < 0.05；0.65±0.89 mg/d，P < 0.05）。B组肾小球基底膜厚度（532±108 nm）和系膜基质密度（56.4±6.8）显著大于其他两组（P < 0.05）。
糖尿病大鼠肾脏中MT3 - MMP和TIMP2 mRNA表达显著增加。氯沙坦可预防糖尿病肾病的发展，并抑制糖尿病大鼠肾脏中MT3 - MMP和TIMP2 mRNA表达。
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