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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 investigate the effect of emodin on the expression of matrix metalloproteinase-2 (MMP-2) / tissue inhibitor of metalloproteinase-2 (TIMP-2) in diabetic rats. Methods The experimental rats were randomly divided into healthy control (NC) group, diabetic model group (DM) and DM + Emodin group (40mg / kg), 12 rats each. All rats were killed by 36 weeks. Blood and urine samples were collected for detection of biochemical indicators and 24hUAlb. Renal tissue samples were taken for detection of related mRNAs and proteins by RT-PCR and Western blot. Results At 36 weeks, the levels of HbA1c (5.6 ± 0.6)% vs (6.44 ± 0.83) vs (33.11 ± 3.02) and (32.39 ± 2.78) mmol / (18 ± 3.2)%, (20.1 ± 3.3)%], SBP [(108 ± 9) vs (131 ± 14), (131 ± 8) mmHg] 11.5 ± 1.0), (10.4 ± 1.3)], eGFR [(5.9 ± 1.2) vs (12.9 ± 2.2), (11.2 ± 1.2) ml / (P <0.001). The ratio of renal weight / body weight, eGFR and UAlb in DM + Emtin group was lower than that in DM group (P <0.05 or P <0.01). Compared with DM group, MMP-2 mRNA in DM + Emodin group was significantly higher than that in DM + Emodin group (1.43 ± 0.36 vs 1.13 ± 0.19, P <0.05), TIMP-2 mRNA 0.001], and the inhibition of 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) The expression level is down. Conclusion Emodin can reduce the expression of MMP-2 / TIMP-2 and proteinuria in the kidney of diabetic rats, which may delay the progression of DN.