中国临床药理学与治疗学2017,Vol.22Issue(8):846-851,6.
川芎嗪对糖尿病肾病大鼠下调HMGB1表达及降低RAGEs作用
Effects of tetramethylpyrazine on the down-regulation of HMGB1 expression and reducing contents of RAGEs in diabetic nephropathy rats
摘要
Abstract
AIM:To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP) on streptozocin (STZ)-induced-nephropathy in type 2 diabetic rats.METHODS:Fifty SD rats were randomly divided into control group (n =10) and model group (n =40).All model rats were fed with high-fat diet for 4 weeks and then injected with streptozotocin (STZ,40 mg/kg,ip).Fasting blood glucose (FBG) was measured by One-Touch glucometer after 72 h.Rats with fasting blood glucose above 16.67 mmoL/L were then randomly divided into four groups:model,metformin (250 mg/kg),low-TMP (80 mg/kg) and high-TMP (160 mg/kg) groups,and the later three received respective drug for 8 weeks,while control and model groups were given equal amount of distilled water by intragastric administration.At the end of the experiment,blood glucose,urine protein,blood urea nitrogen,creatinine,insulin,HOMA-IRI and receptor for advanced glycationend-products (RAGEs) were measured.The expression of high mobility group box 1 (HMGB1) in kidney tissue of rats was determined by immunohistochemistry.Pathological damages of kidney were observed under light microscope.RESULTS:After 8 weeks'administration,compared with the model group,metformin group,low-TMP and high-TMP group showed significant decrease in the dynamic fasting blood glucose (P < 0.01) and urinary protein excretion of total dynamic (P < 0.05 or P <0.01);Metformin and high-TMP can significantly reduce the level of Cr,BUN and RAGEs;the protein expressions of HMGB1 in metformin group and high-TMP group were significantly lower than that in model group (P < 0.05);pathological damages of kidney tissue were significantly reduced.CONCLUSION:TMP exhibited protective effect on STZ induced nephropathy in type 2 diabetic rats and its mechanism may be related to the down-regulation of HGMB1 expression and reducing contents of RAGEs.关键词
川芎嗪/糖尿病肾病/高迁移率族蛋白B1/糖基化终末产物受体Key words
tetramethylpyrazine/diabetic nephropathy/HMGB1/RAGEs分类
医药卫生引用本文复制引用
傅永锦,夏雪怡,张小牧,刘艳波,潘竞锵,吕俊华..川芎嗪对糖尿病肾病大鼠下调HMGB1表达及降低RAGEs作用[J].中国临床药理学与治疗学,2017,22(8):846-851,6.基金项目
广东省科技计划项目(2013B21800034) (2013B21800034)