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目的:通过研究红芪多糖对早期糖尿病肾病(DN)db/db小鼠肾组织中基质金属蛋白酶2(MMP-2)及基质金属蛋白酶组织抑制因子1(TIMP-1)表达的影响,探讨HPS延缓早期DN进展的作用机制。方法:50只SPF级雄性db/db糖尿病肾病模型小鼠用随机数字表法分为5组:红芪多糖200、100、50 mg/kg剂量组、替米沙坦组(5 mg/kg)和模型组(等体积0.9%),每组10只;10只雄性db/m小鼠,作为正常对照组,给予等体积0.9%NS灌胃。所有小鼠在6周龄开始进入实验,连续灌胃8周,于治疗前及治疗后每2周检测血糖浓度,第4周末及第8周末收集小鼠24h尿液,ELISA法检测24h尿微量白蛋白水平。第8周末框后静脉取血,血清用于检测甘油三酯(TG)、总胆固醇(TC)、血清肌酐(Scr)、尿素氮(BUN)。处死小鼠,剥离肾脏,左肾皮质用于RT-PCR、Western blotting检测肾组织MMP-2及TIMP-1 mRNA和蛋白的表达量。结果:与正常组比较,模型组小鼠血糖、血脂、Scr、BUN和24h尿微量白蛋白水平显著升高;MMP-2 mRNA和蛋白的表达水平显著下降,TIMP-1mRNA和蛋白的表达水平明显升高。与模型组比较,各治疗组血糖数值均有所下降,但无统计学意义;除红芪多糖50mg/kg剂量组外,其余各治疗组小鼠血脂、Scr、BUN和24h尿微量白蛋白水平均明显下降;MMP-2 mRNA和蛋白的表达水平明显升高,TIMP-1 mRNA和蛋白的表达水平明显降低,以红芪多糖100mg/kg剂量组疗效最为明显。结论:红芪多糖能够防治db/db小鼠早期DN,其机制可能与红芪多糖抑制TIMP-1并上调MMP-2 mRNA和蛋白在肾脏的表达水平有关。
AIM: To investigate the effect of Radix Hedysari Polysaccharides on the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in kidney of early diabetic nephropathy (DN) db / db mice, Delayed the role of early DN progression mechanism. Methods: Fifty SPF male db / db diabetic nephropathy model mice were randomly divided into five groups: 200,100,50 mg / kg of Hedysarum polysaccharide group, 5 mg / kg of telmisartan group, And model group (equal volume of 0.9%), 10 rats in each group. Ten male db / m mice were given normal 0.9% NS intragastrically. All mice began to enter the experiment at 6 weeks of age and were given gavage continuously for 8 weeks. Blood glucose levels were measured every two weeks before and after treatment. 24h urine was collected at the end of the 4th and the 8th week. Albumin level. At the end of the 8th week, blood was taken from the posterior limbal vein, and the serum was used to detect TG, TC, BUN. The mice were sacrificed, the kidneys were dissected, the left renal cortex was used for RT-PCR, and the expression of MMP-2 and TIMP-1 mRNA and protein in renal tissues was detected by Western blotting. Results: Compared with the normal group, the levels of blood glucose, blood lipids, Scr, BUN and 24h urinary microalbumin in model group were significantly increased; the expression of MMP-2 mRNA and protein was significantly decreased; the expression of TIMP-1 mRNA and protein was significantly Rise. Compared with the model group, the blood glucose value of each treatment group decreased, but not statistically significant; except for the Radix Astragali polysaccharide 50mg / kg dose group, the blood lipids, Scr, BUN and 24h urine microalbumin level Were significantly decreased; the expression of MMP-2 mRNA and protein was significantly increased, the expression of TIMP-1 mRNA and protein was significantly reduced, the most obvious effect of Radix Astragali polysaccharide 100mg / kg dose group. CONCLUSION: Radix Hedysari can prevent early DN of db / db mice, which may be related to the inhibition of TIMP-1 by Hedysarra polysaccharide and the up-regulation of the expression of MMP-2 mRNA and protein in the kidney.