文献类型：期刊文献

中文题名：红芪多糖对早期糖尿病肾病db/db小鼠肾组织中MMP-2及TIMP-1 mRNA和蛋白表达的影响

英文题名：The study on Hedysarum polysacchcaide on the mRNA and protein expressions of MMP-2 and TIMP-1in the kidney tissue of db/db mouse with diabetic nephroma in early stages

作者：金智生[1];魏玉娇[2];林海龙[3];邵晶[1];张花治[1]

第一作者：金智生

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃中医药大学附属医院,兰州730020;[3]甘肃省第二人民医院,兰州730000

第一机构：甘肃中医药大学

年份：2017

卷号：33

期号：4

起止页码：66

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2014】；CSCD:【CSCD2017_2018】；

基金：国家自然科学基金(编号:81160427

语种：中文

中文关键词：红芪多糖;db/db小鼠;糖尿病肾病;MMP-2;TIMP-1

外文关键词：Hedysarum polysacchcaide（红芪多糖）; db/db mice; diabetic nephropathy; MMP-2; TIMP-1

摘要：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。
Objective： The objective of the present study is to explore the mechanisms through which Hedysarum polysacchcaide（ HPS） ameliorates early-stage diabetic nephroma（ DN） by evaluating the effects of HPS on the expression levels of matrix metalloproteinase 2（ MMP-2） and tissue inhibitor of metalloproteinase 1（ TIMP-1） in the kidney tissues of db/db mice with early-stage DN. Method： The total of fifty specific pathogen free（ SPF） db/db mice of DN model aged 6 weeks were divided into 5 groups according to random number table（ n = 10） ： Groups of HPS were gavaged with 200,100,50 mg/kg HPS solution respectively,Telmisartan group was gavaged with 5 mg/kg Telmisartan,Model group was gavaged with 0. 9% NS in equal volume; Control group with ten male 6-week-old db/m mice was gavaged with 0. 9% NS in equal volume. The gavage administration was consecutively performed for 8 weeks. Blood glucose measurement was conducted once before gavage and once every two weeks during gavage. Urine samples for a 24 h duration was collected at the end of the fourth and eighth week for detection of microalbumin by ELISA. At the end of the eighth week,blood was withdrawn from mouse Vena cava for and serum was collected for measuring triglycerides（ TG）,total cholesterol（ TC）,serum creatinine（ Scr）,urea nitrogen（ BUN）. Mice were sacrificed and kidneys were sampled from which the renal cortexes were used for detecting the mRNA and protein levels of MMP-2 and TIMP-1 by RT-PCR and Western blotting. Result： The levels of blood glucose,TG,TC,Scr,BUN and microalbumin in urine samples of 24 h duration were significantly elevated when compared to Control at P〈0. 01. The mRNA and protein levels of MMP-2 and TIMP-1 were significantly downregulated and upregulated at P〈0. 01,respectively. The levels of blood glucose,Scr,BUN and microalbumin in urine samples of 24 h duration were significantly decreased at P〈0. 05 and the levels of mRNA and protein levels of MMP-2 and TIMP-1 were significantly upregulated and downregulated at P〈0. 01 respectively in HPS-treated groups except the 50mg/kg HPS group when compared to Model group. The therapic effect was significantly better in 100mg/kg HPS group than it was in Telmisartan group. Conclusion： HPS is valid in the prevention and treatment of earlystage DN in db/db mouse,probably by upregulating and downregulating the mRNA and protein levels of MMP-2 and TIMP-1 in kidney.