苍术白虎汤对高尿酸血症性肾病小鼠作用机制的研究
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摘要
目的:观察苍术白虎汤对高尿酸血症性肾病模型小鼠的影响并探索其机制。方法:采用腺嘌呤(100mg·kg~(-1))联合乙胺丁醇(250mg·kg~(-1))法制备小鼠高尿酸血症性肾病模型,设立空白组、模型组、苍术白虎汤高、中、低剂量组(6、3、1. 5g·kg~(-1))、苯溴马隆组(20mg·kg~(-1)),连续给药14天。于实验结束后将各组小鼠眼球采血,分光光度法检测其血清中尿酸(BUA)、肌酐(CR)及血浆中尿素氮(BUN)水平,测定血清中黄嘌呤氧化酶(XOD)活性。取双侧肾脏组织匀浆,ELISA法检测肾脏组织中IL-1β、TGF-β1含量。结果:苍术白虎汤可显著降低血清BUA、CR及血浆BUN含量,抑制血清XOD活性及肾脏组织中IL-1β、TGF-β1的表达。结论:苍术白虎汤可通过抑制XOD活性而减少BUA的生成,同时抑制肾脏组织中IL-1β、TGF-β1的表达而发挥对肾脏的保护作用,从而降低BUN及CR的含量。此为苍术白虎汤对高尿酸血症性肾病模型可能的作用机制。
Objective: To observe the curative effect of Cangzhu Baihu Decoction for hyperuricemic nephropathy mice and explore the mechanism. Methods: Animal model was made by Adenine( 100 mg·kg~(-1)) and Ethylamine butanol( 250 mg·kg~(-1)).The animals were divided into normal group,model group,positive drug Benzbromarone( 20 mg·kg~(-1)),the low dose of Cangzhu Baihu Decoction group( 1. 5 g·kg~(-1)),the middle dose( 3 g·kg~(-1)) and high dose( 6 g·kg~(-1)). Then,the drug with different doses was given the medicine,continuously 14 days. At the end of the experiment,the eyeball blood and kidney was collected from each group. Then,the serum level of UA,BUN,CR,XOD and the IL-1β,TGF-β1 in kidney tissue were measured. Results: Compared to the model group,serum BUA,CR,BUN and XOD levels of the Cangzhu Baihu Decoction group was significantly reduced,and downregulated IL-1β,TGF-β1 expression. Conclusion: Cangzhu Baihu Decoction group can reduce BUA production by supressing the activity of XOD. In the meanwhile,Cangzhu Baihu Decoction group can play the protection of the kidney by inhibiting the expressions of IL-1β and TGF-β1 and reduce the serum level of BUN and CR. This is a possible mechanism for the treatment of hyperuricemia nephropathy model by Cangzhu Baihu Decoction group.
Objective: To observe the curative effect of Cangzhu Baihu Decoction for hyperuricemic nephropathy mice and explore the mechanism. Methods: Animal model was made by Adenine( 100 mg·kg~(-1)) and Ethylamine butanol( 250 mg·kg~(-1)).The animals were divided into normal group,model group,positive drug Benzbromarone( 20 mg·kg~(-1)),the low dose of Cangzhu Baihu Decoction group( 1. 5 g·kg~(-1)),the middle dose( 3 g·kg~(-1)) and high dose( 6 g·kg~(-1)). Then,the drug with different doses was given the medicine,continuously 14 days. At the end of the experiment,the eyeball blood and kidney was collected from each group. Then,the serum level of UA,BUN,CR,XOD and the IL-1β,TGF-β1 in kidney tissue were measured. Results: Compared to the model group,serum BUA,CR,BUN and XOD levels of the Cangzhu Baihu Decoction group was significantly reduced,and downregulated IL-1β,TGF-β1 expression. Conclusion: Cangzhu Baihu Decoction group can reduce BUA production by supressing the activity of XOD. In the meanwhile,Cangzhu Baihu Decoction group can play the protection of the kidney by inhibiting the expressions of IL-1β and TGF-β1 and reduce the serum level of BUN and CR. This is a possible mechanism for the treatment of hyperuricemia nephropathy model by Cangzhu Baihu Decoction group.
引文
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[2]杨媛,李静,甄健存,等.抗痛风药别嘌呤醇、苯溴马隆及秋水仙碱不良反应报告分析[J].中国医院药学杂志,2013,33(15):1296~1297
[3]杜霄壤,高建东.高尿酸血症肾病的中医药研究[J].长春中医药大学学报,2012,28(02):264~266
[4]曾菁蓉.中西医结合治疗高尿酸血症肾病46例[J].光明中医,2008,(08):1114~1115
[5]杨秀飞,黄传兵,徐慧敏,等.中医辨治痛风性肾病的研究现状[J].风湿病与关节炎,2017,6(03):73~76
[6]杨帆,战世宇,刁建炜,等.苍术白虎汤干预急性痛风性关节炎大鼠的疗效及机制探讨[J].中医药导报,2017,18:53~55
[7]张保国,程铁锋,刘庆芳.白虎汤药效及现代临床研究[J].中成药,2009,31(08):1272~1275
[8]李宇馨,李瑞海.苍术挥发油抗炎活性研究[J].辽宁中医药大学学报,2013,15(2):71~72
[9]赵海霞,徐向东.白虎汤的抗炎作用及其作用机理的研究[J].时珍国医国药,2013,24(1):60~62
[10]汪年松,桂定坤.尿酸性肾病的中西医结合治疗进展[J].中华肾病研究电子杂志,2015,4(02):10~14.[2017~08~10][11] Roughley MJ,Belcher J,Mallen CD,et al. Gout and risk ofchronic kidney disease and nephrolithiasis:me-ta-analysis of observationalstudies[J]. Arthritis Res Ther,2015,17(1):90
[12] Fu W,Li Q,Yao J,et al. Protein expression of urate trans-porters in renal tissue of patients with uric acid nephrolithiasis[J]. CellBiochem Biophys,2014,70(1):449~454
[13]程芳,戴敏,胡翠云,等.痛风康对酵母膏致高尿酸血症大鼠尿酸代谢及黄嘌呤氧化酶活性的影响[J].安徽中医学院学报,2011,30(04):55~58
[14] Tosu A R,Demir S,Selcuk M,et al. Comparison of inflam-matory markers in non-dipper hypertension vs. dipper hypertension and innormotensive individuals:uricacid,C-reactive protein and red blood celldistributionwidth readings[J]. Postepy Kardiol Interwencyjnej,2014,10(2):98~103
[15]肖琦,慎田田,李雅君,等.中医药抗肾纤维化中以TGF-β1为靶点的研究进展[J].河南中医,2011,31(03):305~307