土茯苓治疗小鼠高尿酸血症的机制研究
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摘要
目的:探讨土茯苓(rhizoma smilacis glabrae)对小鼠高尿酸血症模型的肾脏保护作用及机制。方法:采用次黄嘌加氧嗪酸钾灌胃建立高尿酸血症小鼠模型,随机分为4组:正常、模型、别嘌呤醇和土茯苓组。检测各组血清尿酸、肌酐、尿素氮水平,肝脏黄嘌呤氧化酶(XOD)活性,肾脏尿酸转运体(URAT1、GLUT9) mRNA和蛋白表达水平,肾组织IL-1β和TNF-α水平。结果:土茯苓可显著降低高尿酸血症小鼠血清尿酸、肌酐和尿素氮,同时可抑制XOD活性,显著下调肾脏URAT1、GLUT9的mRNA和蛋白表达,抑制IL-1β、TNF-α表达。结论:土茯苓可明显改善小鼠高尿酸血症和肾功能下降,作用机制可能通过抑制XOD活性,调节尿酸转运体的水平,及抑制炎症因子的表达实现的。
Objective: To investigate the renal protective effect of Rhizoma smilacis glabrae on hyperuricemia in mice and its mechanism. Methods: A mouse model of hyperuricemia was established by intragastric administration of hypoxanthine and potassium oxonate. They were randomly divided into 4 groups: normal,model,positive drug control( allopurinol) and Rhizoma smilacis glabrae group. Serum uric acid,creatinine and urea nitrogen levels were measured,hepatic xanthine oxidase( XOD) activities,mRNA and protein expressions of renal urate transpoters( URAT1,GLUT9) and leves of IL-1β,TNF-αin renal tissue were analyzed. Results:Rhizoma smilacis glabrae can significantly reduce serum uric acid,creatinine and urea nitrogen levels in hyperuricemia mice,inhibit liver XOD activity,and down-regulate the expression of renal URAT1,GLUT9 mRNA and protein expressions,inhibit the expression of inflammatory factors IL-1β and TNF-α in renal tissure. Conclusion: Rhizoma smilacis glabrae has a significant improvement effect on the animal model of hyperuricemia in mice. The mechanism may be achieved by inhibiting XOD activity,regulating expression of renal urate transpoters and inhibiting the expression of inflammatory factors.
Objective: To investigate the renal protective effect of Rhizoma smilacis glabrae on hyperuricemia in mice and its mechanism. Methods: A mouse model of hyperuricemia was established by intragastric administration of hypoxanthine and potassium oxonate. They were randomly divided into 4 groups: normal,model,positive drug control( allopurinol) and Rhizoma smilacis glabrae group. Serum uric acid,creatinine and urea nitrogen levels were measured,hepatic xanthine oxidase( XOD) activities,mRNA and protein expressions of renal urate transpoters( URAT1,GLUT9) and leves of IL-1β,TNF-αin renal tissue were analyzed. Results:Rhizoma smilacis glabrae can significantly reduce serum uric acid,creatinine and urea nitrogen levels in hyperuricemia mice,inhibit liver XOD activity,and down-regulate the expression of renal URAT1,GLUT9 mRNA and protein expressions,inhibit the expression of inflammatory factors IL-1β and TNF-α in renal tissure. Conclusion: Rhizoma smilacis glabrae has a significant improvement effect on the animal model of hyperuricemia in mice. The mechanism may be achieved by inhibiting XOD activity,regulating expression of renal urate transpoters and inhibiting the expression of inflammatory factors.
引文
1. Deeks ED. Lesinurad:A Review in Hyperuricaemia of Gout.Drugs&Aging,2017,34(5):1-10.
2 .朱辟疆,刁金囡.尿酸性肾病的中西医研究和治疗进展.中国中西医结合肾病杂志,2015,16(1):74-77.
3 .张娴娴,孙维峰,侯燕,等.复方土茯苓颗粒治疗高尿酸血症40 例随机对照临床观察.中医杂志,2016,57(1):41-45.
4 .刘金畅,王涛.萆薢、土茯苓治疗高尿酸血症研究进展.辽宁中医药大学学报,2018(1):79-81.
5 .尹非,李雪晨,叶菲.高尿酸血症与代谢综合征研究进展.国际药学研究杂志,2017,44(6):487-490.
6 .曾楚楚,范瑛,汪年松.高尿酸血症与慢性肾脏病关系的研究进展.中国中西医结合肾病杂志,2016,17(2):167-169.
7 .刘金畅,王涛.治疗高尿酸血症药物研发现状与思考.天津中医药,2017,34(5):291-294.
8 .朱祥祥,方颖莹,庞敏霞,等.不同造模因素复制小鼠高尿酸血症模型的比较研究.浙江中医药大学学报,2018(2).
9 .周洁,孙超,李飞.中药活性成分降尿酸作用机制研究进展.中国药理学通报,2018(1):19-22.
10.徐婷婷,承志凯,尹莲,等.土茯苓抑制黄嘌呤氧化酶活性的物质基础研究.中药材,2012,35(4):582-585.
11 .吴新荣,臧路平,刘志刚.抗高尿酸血症药物作用靶点研究进展.中国药理学通报,2010,26(11):1414-1417.
12 . Enomoto A,Endou H. Roles of organic anion transporters(OATs)and a urate transporter(URAT1)in the pathophysiology of human disease. Clinical&Experimental Nephrology,2005,9(3):195-205.
13 . Preitner F,Bonny O,Laverrière A,et al. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proceedings of the National Academy of Sciences of the United States of America,2009,106(36):15501-15506.
14 . Schweyer S,Hemmerlein B,Radzun HJ,et al. Continuous recruitment,co-expression of tumour necrosis factor-αand matrix metalloproteinases,and apoptosis of macrophages in gout tophi. Virchows Archiv,2000,437(5):534-539.
15 .王环芬,陈大庆.土茯苓萆薢方联合美洛昔康片对急性痛风性关节炎患者IL-1β及NF-κBp65表达的影响.新中医,2016,(7):122-124.
2 .朱辟疆,刁金囡.尿酸性肾病的中西医研究和治疗进展.中国中西医结合肾病杂志,2015,16(1):74-77.
3 .张娴娴,孙维峰,侯燕,等.复方土茯苓颗粒治疗高尿酸血症40 例随机对照临床观察.中医杂志,2016,57(1):41-45.
4 .刘金畅,王涛.萆薢、土茯苓治疗高尿酸血症研究进展.辽宁中医药大学学报,2018(1):79-81.
5 .尹非,李雪晨,叶菲.高尿酸血症与代谢综合征研究进展.国际药学研究杂志,2017,44(6):487-490.
6 .曾楚楚,范瑛,汪年松.高尿酸血症与慢性肾脏病关系的研究进展.中国中西医结合肾病杂志,2016,17(2):167-169.
7 .刘金畅,王涛.治疗高尿酸血症药物研发现状与思考.天津中医药,2017,34(5):291-294.
8 .朱祥祥,方颖莹,庞敏霞,等.不同造模因素复制小鼠高尿酸血症模型的比较研究.浙江中医药大学学报,2018(2).
9 .周洁,孙超,李飞.中药活性成分降尿酸作用机制研究进展.中国药理学通报,2018(1):19-22.
10.徐婷婷,承志凯,尹莲,等.土茯苓抑制黄嘌呤氧化酶活性的物质基础研究.中药材,2012,35(4):582-585.
11 .吴新荣,臧路平,刘志刚.抗高尿酸血症药物作用靶点研究进展.中国药理学通报,2010,26(11):1414-1417.
12 . Enomoto A,Endou H. Roles of organic anion transporters(OATs)and a urate transporter(URAT1)in the pathophysiology of human disease. Clinical&Experimental Nephrology,2005,9(3):195-205.
13 . Preitner F,Bonny O,Laverrière A,et al. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proceedings of the National Academy of Sciences of the United States of America,2009,106(36):15501-15506.
14 . Schweyer S,Hemmerlein B,Radzun HJ,et al. Continuous recruitment,co-expression of tumour necrosis factor-αand matrix metalloproteinases,and apoptosis of macrophages in gout tophi. Virchows Archiv,2000,437(5):534-539.
15 .王环芬,陈大庆.土茯苓萆薢方联合美洛昔康片对急性痛风性关节炎患者IL-1β及NF-κBp65表达的影响.新中医,2016,(7):122-124.