【摘要】  目的   探讨大黄素对糖尿病大鼠肾组织基质金属蛋白酶-2（MMP-2）/金属蛋白酶组织抑制剂-2(TIMP-2)表达的影响。  方法    实验大鼠随机分为健康对照（NC）组、糖尿病模型（DM）组及大黄素治疗(DM+Emodin)组（40 mg/kg），各12只。至36周时处死所有大鼠，收集血、尿标本，检测生化指标和24 hUAlb；取肾组织标本，采用RT-PCR和Western blot检测相关mRNA及蛋白。  结果  36周时，与NC组比较，DM组和DM+Emodin组血糖[（33.11±3.02)，(32.39±2.78) vs (6.44±0.83) mmol/L]、HbA1c[（18.0±3.2)%，（20.1±3.3）% vs (5.6±0.6)%]、SBP[（131±14),(131±8) vs (108±9) mmHg]、肾重/体重比[（11.5±1.0),(10.4±1.3) vs (5.3±0.6)]、eGFR[（12.9±2.2)，(11.2±1.2) vs (5.9±1.2) [ml/（min·173 m²）]及UAlb[（52.8±30.1)，(26.6±10.5) vs （3.3±1.8） mg/24 h]升高（P＜0.001），DM+Emtin组肾重/体重比、eGFR及UAlb均低于DM组(P＜0.05或P＜0.01)。与DM组比较，DM+Emodin组MMP-2 mRNA[（1.43±0.36) vs （1.13±0.19），P＜0.05]、TIMP2 mRNA[（1.70±0.27) vs （1.23±0.18），P＜0.001]上调现象被抑制，且MMP-2[(2.45±0.24) vs (2.98±0.55), P＜0.01]、TIMP-2[(2.07±0.30) vs (1.59±0.37), P＜0.001]蛋白表达水平下调。  结论  大黄素可以减少糖尿病大鼠肾组织中的MMP-2/TIMP-2表达，减少蛋白尿，可能延缓DN进展。

    【关键词】  基质金属蛋白酶-2；金属蛋白酶组织抑制剂-2；糖尿病；糖尿病肾病；大黄素

    Effect of Emodin on the expressions of MMP-2 /TIMP 2 in the renal tissue of rats 

with diabetes

     【Abstract】  Objective  To observe the expressions of matrix metalloproteinase-2 (MMP-2)/tissue inhibi-tor of matrix metalloproteinase-2(TIMP-2) in the renal tissue of rats with diabetes (DM) and to investigate the effect of emodin on the expressions of MMP-2/TIMP-2.  Methods   24 DM model rats were randomly divided into diabetes(DM, n=12) group or emodin-treatment(DM+Emodin, n=12, with Emodin 40 mg/kg) group. 12 normal control rats were set as NC group. The rats were sacrificed at 36 weeks. Blood and urine samples were collected to detect biochemical indices and 24 h UAlb. RT-PCR and western blot were used to detect the expressions of MMP-2/TIMP-2 in renal tissue.  Results   Compared with NC group, the levels of blood glucose[（33.11±3.02), (32.39±2.78) vs (6.44±0.83) mmol/L], HbA1c[（18.0±3.2)%,（20.1±3.3）% vs (5.6±0.6)%], SBP[（131±14),(131±8) vs (108±9) mmHg], KW/BW[(11.5±1.0),(10.4±1.3) vs (5.3±0.6)], eGFR（12.9±2.2)，(11.2±1.2) vs (5.9±1.2)ml/（min·173 m²）]﹜ and UAlb[（52.8±30.1)，(26.6±10.5) vs （3.3±1.8） mg/24 h] were markedly increased in DM group and DM+Emodin group （all P＜0.001）. All of these changes were less when DM+Emodin group compared with DM group（all P＜0.05）. Compared with DM group, the up-regulation of MMP-2[（1.43±0.36) vs （1.13±0.19）， P＜0.05] and TIMP-2 mRNA expression [（1.70±0.27) vs （1.23±0.18），P＜0.001] in DM+Emodin group were sup-pressed. The DM+Emodin group showed down-regulated MMP-2[(2.45±0.24) vs (2.98±0.55), P＜0.01] and TIMP-2[(2.07±0.30) vs (1.59±0.37), P＜0.001] protein expression, that consistent with RT-PCR results.  Conclusion  Emodin plays a role in reducing proteinuria and delaying the development of diabetic nephropathy through down-regulating MMP2/TIMP-2 expression．

    【Key words】 Matrix metalloproteinase-2（MMP-2）; Tissue inhibitor of matrix metalloproteinase-2(TIMP-2); Diabetes mellitus; Diabetic nephropathy; Emodin