大黄素对糖尿病大鼠肾组织基质金属蛋白酶-2及金属蛋白酶组织抑制剂-2表达的影响  

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

作　　者：杨秀[1] 马立彬[1] 谢祥成[1] 张波[2] 杨明[2] 费晓[1] 程明[2] 王鸣[1] 梅长林[2] 

机构地区：[1]杭州市第一人民医院肾内科,310062 [2]第二军医大学附属长征医院肾内科

出　　处：《中国糖尿病杂志》2016年第2期159-162,共4页Chinese Journal of Diabetes

基　　金：杭州市科技计划重点专科专病项目(20140733Q07)

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(40mg/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24hUAlb;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[(6.44±0.83)vs(33.11±3.02),(32.39±2.78)mmol/L]、HbA1c[(5.6±0.6)%vs(18.0±3.2)%,(20.1±3.3)%]、SBP[(108±9)vs(131±14),(131±8)mmHg]、肾重/体重比[(5.3±0.6)vs(11.5±1.0),(10.4±1.3)]、eGFR[(5.9±1.2)vs(12.9±2.2),(11.2±1.2)ml/(min·173m2)]及UAlb[(3.3±1.8)vs(52.8±30.1),(26.6±10.5)mg/24h]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]、TIMP-2 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MMP-2/TIMP-2表达,减少蛋白尿,可能延缓DN进展。Objective To observe the expressions of matrix metalloproteinase-2（MMP-2）/tissue inhibitor 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 40mg/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 hUAlb.RT-PCR and western blot were used to detect the expressions of MMP-2/TIMP-2in renal tissue. Results Compared with NC group,the levels of blood glucose[（6.44±0.83）vs（33.11±3.02）,（32.39±2.78）mmol/L],HbA1c[（5.6±0.6）% vs（18.0±3.2）%,（20.1±3.3）%],SBP[（108±9）vs（131±14）,（131±8）mmHg],KW/BW[（5.3±0.6）vs（11.5±1.0）,（10.4±1.3）],eGFR[（5.9±1.2）vs（12.9±2.2）,（11.2±1.2）ml/（min·173 m2）]and UAlb[（3.3±1.8）vs（52.8±30.1）,（26.6±10.5）mg/24h]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 upregulation of MMP-2[（1.43±0.36）vs（1.13±0.19）,P〈0.05]and TIMP-2mRNA expression [（1.70±0.27）vs（1.23±0.18）,P〈0.001]in DM＋Emodin group were suppressed.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. ConclusionEmodin plays a role in reducing proteinuria and delaying the development of diabetic nephropathy through down-regulating MMP-2/TIMP-2expression.

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 

分 类 号：R587.2[医药卫生—内分泌]