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中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (8): 846-851.

• 基础研究 • 上一篇    下一篇

川芎嗪对糖尿病肾病大鼠下调HMGB1表达及降低RAGEs作用

傅永锦1,夏雪怡2,张小牧1,刘艳波2,潘竞锵1,吕俊华3   

  1. 1广州市中医医院药学部,广州 510130,广东; 2北华大学基础医学院病理生理学教研室,吉林 130021,吉林; 3暨南大学药学院药理学教研室,广州 510632,广东
  • 收稿日期:2017-04-06 修回日期:2017-05-06 出版日期:2017-08-26 发布日期:2017-08-18
  • 通讯作者: 潘竞锵,男,主任药师,主要从事抗炎-免疫、老年药学和生化药理学研究。 E-mail: pjq56@yahoo.com.cn
  • 作者简介:傅永锦,男,副主任药师,主要从事药学研究。 Tel: 020-81226275 E-mail: jin498@126.com
  • 基金资助:

    广东省科技计划项目(2013B21800034)

Effects of tetramethylpyrazine on the down-regulation of HMGB1 expression and reducing contents of RAGEs in diabetic nephropathy rats

FU Yongjin 1, XIA Xueyi 2, ZHANG Xiaomu 1, LIU Yanbo 2, PAN Jingqiang 1, LV Junhua 3   

  1. 1 Department of Pharmacy, Guangzhou Traditional Chinese Medical Hospital, Guangzhou 510130, Guangdong, China; 2 Department of Pathophysiology, School of Basic Medical Sciences, Beihua University,Jilin 132001, Jilin, China; 3 Teaching and Research Section of Pharmacology, Pharmacy College, Jinan University, Guangzhou 510632, Guangdong, China
  • Received:2017-04-06 Revised:2017-05-06 Online:2017-08-26 Published:2017-08-18

摘要:

目的: 探讨川芎嗪对链脲佐菌素诱导2型糖尿病大鼠肾病的治疗作用及机制。方法: SD大鼠50只,随机分为正常组和模型组。除正常组外,其余大鼠均给予高脂-高糖饲料喂养4周,再给予链脲佐菌素(40 mg/kg,ip),72 h后测定空腹血糖,将血糖值高于16.67 mmol/L的大鼠随机分成4个组,即模型组,二甲双胍阳性组(250 mg/kg),川芎嗪低(80 mg/kg)、高剂量组(160 mg/kg),连续给予相应试药8周。其中正常组和模型组的大鼠均给予同等量蒸馏水灌胃。实验结束时,测定大鼠血糖、尿蛋白、血尿素氮、血肌酐、胰岛素、胰岛素抵抗指数和糖基化终末产物受体(receptor for advanced glycation end-products,RAGEs)含量;免疫组化法测定大鼠肾组织高迁移率族蛋白B1(high mobility group box 1,HMGB1)蛋白表达,光镜下观察肾脏病理学变化。结果: 与模型组比较,二甲双胍和高、低剂量川芎嗪给药8周后,均能明显降低大鼠动态空腹血糖(P<0.01),动态尿蛋白总排出量显著降低(P<0.05或P<0.01);二甲双胍及高剂量川芎嗪均能明显降低大鼠肌酐,尿素氮及RAGEs含量(P<0.05或P<0.01);二甲双胍组和高剂量川芎嗪组HMGB1蛋白表达明显低于模型组(P<0.05);肾脏组织病理性损伤明显减轻。结论:川芎嗪对链脲佐菌素诱导2型糖尿病大鼠早期肾病具有保护作用,其机制可能与下调HMGB1表达作用及降低RAGEs作用有关。

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

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.

Key words:  tetramethylpyrazine, diabetic nephropathy, HMGB1, RAGEs

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