二妙丸不同配伍比例对大鼠高尿酸血症的影响
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摘要
[目的]研究二妙丸不同配伍比例对高尿酸血症大鼠尿酸的影响。[方法]采用酵母膏15 g/kg+腺嘌呤100 mg/kg+氧嗪酸钾300 mg/kg联合用药制备大鼠高尿酸血症模型。将100只雄性SD大鼠随机分为10组,分别是空白对照组、模型组、苍术∶黄柏1∶1组(简称苍黄1∶1组)、苍术∶黄柏1∶2组(苍黄1∶2组)、苍术∶黄柏2∶1组(苍黄2∶1组)、苍术∶黄柏1∶3组(苍黄1∶3组)、苍术∶黄柏3∶1组(苍黄3∶1组)、苍术∶黄柏1∶0组(苍黄1∶0组)、苍术:黄柏0∶1组(苍黄0∶1组)、阳性药组(别嘌呤醇15 mg/kg)。除空白对照组给予同体积生理盐水外,其他各组大鼠分别连续7 d给予酵母膏15 g/kg+腺嘌呤100 mg/kg灌胃造模,同时各比例组给予生药4.8 g/kg二妙丸,于最后1 d灌胃1次氧嗪酸钾300 mg/kg 1次,1 h后取材,通过检测大鼠血清尿酸(BUA)、黄嘌呤氧化酶(XOD)、肌酐(SCr)、尿素氮(BUN)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆固醇(T-CHO)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)水平,观察大鼠尿液中尿肌酐(UCr)、尿尿素氮(UUN)、24 h尿量(24 h UV)、24 h尿酸排泄量(24 h UUA)水平,及肝肾质量和肝肾脏器系数,研究二妙丸不同配伍比例对大鼠高尿酸血症的影响。[结果]与模型组比较,二妙丸各比例治疗组及阳性药组大鼠的BUA、XOD(除苍黄3∶1、1∶0、0∶1组)、SCr、24 h UV(除苍黄0∶1组、阳性药组)、24 h UUA、T-CHO、TG(除阳性药组)、HDL-C、LDL-C、肝脏质量及肝脏脏器系数(除阳性药组)、肾脏质量和肾脏脏器系数水平显著降低(P<0.05或P<0.01)。与模型组比较,各治疗组均能显著提高大鼠UCr(除苍黄1∶0组)、UUN(除苍黄3∶1组)水平(P<0.05或P<0.01),而大鼠ALT(除苍黄1∶2组)、AST水平有升高趋势但并无显著性差异(P>0.05)。[结论]综合以上指标,初步表明二妙丸不同配伍比例具有显著降低高尿酸血症大鼠BUA、XOD水平并促进肾脏尿酸排泄、改善肾功能、调节血脂水平的作用,其中苍黄1∶2组效果较为显著。
[Objective] To investigate the effects of Ermiao Pill for different compatibility proportion on the treatment of hyperuricemic SD rats. [Methods] Using yeast extract 15 g/kg + adenine oxazine 100 mg/kg + oxygen acid potassium 300 mg/kg combination in the preparation of high uric acid hematic disease model in rats. 100 male rats were randomly divided into 10 groups, respectively is the blank group, model group, rhizoma atractylodis, cortex phellodendri, 1 ∶ 1 group, rhizoma atractylodis, cortex phellodendri, 1 ∶ 2 group, rhizoma atractylodis, cortex phellodendri, 2 ∶1, rhizoma atractylodis, cortex phellodendri, 1 ∶3 group, rhizoma atractylodis, cortex phellodendri group 3 ∶1 group, the rhizoma atractylodis, cortex phellodendri, 1 ∶0, rhizoma atractylodis, cortex phellodendri 0 ∶1group, positive drug group(allopurinol 15 mg/kg). Groups respectively ig give rats 1 week in a row, after the last delivery, by detecting the serum concentration of UA, Cre, BUN, serum ALT, AST, T-CHO, TG, HDL, LDL-C-C level, observed in the urine of rats 24 h uua, Cre, BUN, 24 h uv, and quality of liver, kidney and coefficient,evaluation of Ermiao Pill for different compatibility of uric acid. [Results] Compared with model group, Ermiao Pill rate in treatment group and positive medicine group of rats serum uric acid levels were significantly lower(P<0.01),of which highlights 1∶2 group effect is significant. Compared with model control group, serum creatinine, 24 h urine(except highlights 1 ∶0 group, positive drug group), 24 h level of uric acid excretion, kidney, kidney coefficient of quality level increased significantly(P<0.05 or P<0.01), urinary creatinine and urea nitrogen levels(except group highlights 3 ∶1), 24 h urine uric acid decreased significantly(P <0.05 or P <0.01). Compared with model group, the proportion of groups and positive medicine group can improve the level of ALT and AST of rats but no significant difference(P >0.05), the quality of the liver and liver coefficient in addition to the positive medicine group were significantly lower than model group(P <0.05 or P <0.01). Compared with model group, in addition to the positive medicine group failed to significantly reduce the TG level(P>0.05), and the rest of the group can significantly reduce the T-CHO, TG, HDL, LDL-C level(P <0.05 or P <0.01). [Conclusion] Ermiao Pill for different compatibility proportion have significantly reduced the high uric acid hematic disease uric acid levels in rats and improve renal uric acid excretion, renal function, the function of regulating blood lipid level. Especially highlights 1 ∶2 group effect is significant, and is superior to other groups.
[Objective] To investigate the effects of Ermiao Pill for different compatibility proportion on the treatment of hyperuricemic SD rats. [Methods] Using yeast extract 15 g/kg + adenine oxazine 100 mg/kg + oxygen acid potassium 300 mg/kg combination in the preparation of high uric acid hematic disease model in rats. 100 male rats were randomly divided into 10 groups, respectively is the blank group, model group, rhizoma atractylodis, cortex phellodendri, 1 ∶ 1 group, rhizoma atractylodis, cortex phellodendri, 1 ∶ 2 group, rhizoma atractylodis, cortex phellodendri, 2 ∶1, rhizoma atractylodis, cortex phellodendri, 1 ∶3 group, rhizoma atractylodis, cortex phellodendri group 3 ∶1 group, the rhizoma atractylodis, cortex phellodendri, 1 ∶0, rhizoma atractylodis, cortex phellodendri 0 ∶1group, positive drug group(allopurinol 15 mg/kg). Groups respectively ig give rats 1 week in a row, after the last delivery, by detecting the serum concentration of UA, Cre, BUN, serum ALT, AST, T-CHO, TG, HDL, LDL-C-C level, observed in the urine of rats 24 h uua, Cre, BUN, 24 h uv, and quality of liver, kidney and coefficient,evaluation of Ermiao Pill for different compatibility of uric acid. [Results] Compared with model group, Ermiao Pill rate in treatment group and positive medicine group of rats serum uric acid levels were significantly lower(P<0.01),of which highlights 1∶2 group effect is significant. Compared with model control group, serum creatinine, 24 h urine(except highlights 1 ∶0 group, positive drug group), 24 h level of uric acid excretion, kidney, kidney coefficient of quality level increased significantly(P<0.05 or P<0.01), urinary creatinine and urea nitrogen levels(except group highlights 3 ∶1), 24 h urine uric acid decreased significantly(P <0.05 or P <0.01). Compared with model group, the proportion of groups and positive medicine group can improve the level of ALT and AST of rats but no significant difference(P >0.05), the quality of the liver and liver coefficient in addition to the positive medicine group were significantly lower than model group(P <0.05 or P <0.01). Compared with model group, in addition to the positive medicine group failed to significantly reduce the TG level(P>0.05), and the rest of the group can significantly reduce the T-CHO, TG, HDL, LDL-C level(P <0.05 or P <0.01). [Conclusion] Ermiao Pill for different compatibility proportion have significantly reduced the high uric acid hematic disease uric acid levels in rats and improve renal uric acid excretion, renal function, the function of regulating blood lipid level. Especially highlights 1 ∶2 group effect is significant, and is superior to other groups.
引文
[1]梁晓萍,梁琼麟,胡坪,等.高尿酸血症与痛风研究进展[J].中国药理学通报,2008,24(10):1265-1268.
[2]邵继红,徐耀初,莫宝庆,等.痛风与高尿酸血症的流行病学研究进展[J].疾病控制杂志,2004,8(2):152-154.
[3]潘志,段富津,王颖航,等.黄柏与苍术提取物对高尿酸血症小鼠血尿酸的影响[J].时珍国医国药,2008,19(1):112-113.
[4]Iseki K,Ikemiya Y,Inoue T,et al.significance of hypemricemia as a risk factor for developing ESRD in a screened cohort[J].Am J Kidlley Dis,2004,44(4):642.
[5]Sundstrom J,Sullivan L,D’Agostlno RB,et a1.Relatious of serum uric acid to longitudinal blood pressure tracking and hypertention incidence[J].Hypartention,2005,45(1):18.
[6]朱君,余俊文.高尿酸血症和痛风的流行病学及其危险因素的研究进展[J].现代生物医学进展,2008,8(8):191-195.
[7]陈光亮,徐叔云.高尿酸血症研究进展[J].中国药理学通报,2003,19(10):1088-1092.
[8]叶任高,陆再英,谢毅,等.内科学[M].第6版.北京:人民卫生出版社,2004:865.
[9]Min HK,Lee B,Kwok SK,et al.Allopurinol hypersensitivity syndrome in patients with hematological malignancies:characteristics and clinical outcomes[J].The Korean Journal of Internal Medicine,2015,30(4):521-530.
[10]安雅婷,杨培树,王雅琦,等.高尿酸血症发病机制及药物治疗[J].天津药学,2015,27(5):72-75.
[11]谢建翔.别嘌呤醇严重不良反应19例分析[J].药学与临床研究,2013,21(1):94-95.
[12]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.
[13]王曙光,李成建.别嘌呤醇不良反应[J].中国误诊学杂志,2004,4(6):947.
[14]黄玉斌.381例别嘌醇不良反应分析[J].中国药物应用与监测,2005,2(1):32-34.
[15]傅得兴.别嘌醇的不良反应及安全应用[J].药物不良反应杂志,2003,5(3):173-176.
[16]蔡泳,陈雪观.别嘌醇致严重不良反应分析[J].医药导报,2012,31(2):264-266.
[17]李新强,王丽英.中医药治疗高尿酸血症的研究进展[J].中国实验方剂学杂志,2011,17(3):226-228.
[18]朱春胜,张冰,林志健,等.中医药治疗高尿酸血症的研究进展[J].中华中医药杂志,2015,12(6):4374-4376.
[19]焦剑.中医药治疗高尿酸血症的研究进展[J].天津中医药,2014,31(6):379-381.
[20]张宸,李君玲,田佳星,等.高尿酸血症的中医药治疗研究进展[J].中国新药杂志,2013,22(6):670-673.
[21]李琳,张敏,李苒,等.中药治疗高尿酸血症实验研究进展[J].天津中医药,2013,30(3):190-192.
[22]李莉,田甜,应森林.痛风性关节炎的中医药治疗进展[J].天津中医药大学学报,2013,32(4):253-255.
[23]徐晨,刘舒,刘志强,等.离心超滤质谱法筛选中药复方二妙丸中黄嘌呤氧化酶抑制剂[J].高等学校化学学报,2014,35(8):1640-1645.
[24]唐诗韵,万雪梅,贾琴,等.二妙散系列方治疗痛风的系统评价[J].中药药理与临床,2014,30(6):198-202.
[25]陈维佳,武毅,徐晨,等.紫外可见光谱及成像方法研究二妙丸药物对高尿酸血症疗效的影响[J].光谱学与光谱分析,2015,35(4):956-960.
[26]吕耀中,胡庆华,王星,等.二妙丸水提取物对高尿酸血症小鼠尿酸失衡及其相关基因和蛋白水平的影响[J].中草药,2010,41(3):418-423.
[27]熊湘明,田凤石,姜霞,等.二妙散加减方对实验性高尿酸血症肾损害的保护作用[J].天津医科大学学报,2007,13(1):90-92.
[28]王晗,张敏,路腾飞,等.高尿酸血症动物模型研究进展[J].天津中医药大学学报,2014,33(4):253-256.
[29]孟笑玮,樊克涛,代向东,等.高尿酸血症动物模型的实验研究[J].天津中医药,2015,32(10):614-617.
[30]刘淑芬,曾学军.高尿酸血症动物模型研究进展[J].基础医学与临床,2011,31(3):344-347.
[31]马思佳,霍娇,张立实.高尿酸血症动物模型研究进展[J].卫生研究,2015,44(1):158-162.
[32]彭仙娥,黄之敏,黄萌,等.高尿酸血症与代谢综合征关系[J].中国公共卫生,2009,25(9):1088-1089.
[33]李京.高尿酸血症与代谢综合征关系的研究[D].潍坊:潍坊医学院,2014.
[34]Akkasilpa S,Avihingsanon Y,Hanvivadhanakul P,et al.Clinicalmani-festations of patients with hyperuricemia[J].Journal of the Medical Association of Thailand,2004,87(Suppl2):S41.
[35]Keiiehi S,Shinichi K,Yuji I,et al.Determination of atractylon in Atraetylodes rhizome using supercritieal fluid ehromatography 011-line coupled with supereritical fluid extraction by the direct induefion method[J].Journal of Chromatography A,1998,810(1-2):252.
[2]邵继红,徐耀初,莫宝庆,等.痛风与高尿酸血症的流行病学研究进展[J].疾病控制杂志,2004,8(2):152-154.
[3]潘志,段富津,王颖航,等.黄柏与苍术提取物对高尿酸血症小鼠血尿酸的影响[J].时珍国医国药,2008,19(1):112-113.
[4]Iseki K,Ikemiya Y,Inoue T,et al.significance of hypemricemia as a risk factor for developing ESRD in a screened cohort[J].Am J Kidlley Dis,2004,44(4):642.
[5]Sundstrom J,Sullivan L,D’Agostlno RB,et a1.Relatious of serum uric acid to longitudinal blood pressure tracking and hypertention incidence[J].Hypartention,2005,45(1):18.
[6]朱君,余俊文.高尿酸血症和痛风的流行病学及其危险因素的研究进展[J].现代生物医学进展,2008,8(8):191-195.
[7]陈光亮,徐叔云.高尿酸血症研究进展[J].中国药理学通报,2003,19(10):1088-1092.
[8]叶任高,陆再英,谢毅,等.内科学[M].第6版.北京:人民卫生出版社,2004:865.
[9]Min HK,Lee B,Kwok SK,et al.Allopurinol hypersensitivity syndrome in patients with hematological malignancies:characteristics and clinical outcomes[J].The Korean Journal of Internal Medicine,2015,30(4):521-530.
[10]安雅婷,杨培树,王雅琦,等.高尿酸血症发病机制及药物治疗[J].天津药学,2015,27(5):72-75.
[11]谢建翔.别嘌呤醇严重不良反应19例分析[J].药学与临床研究,2013,21(1):94-95.
[12]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.
[13]王曙光,李成建.别嘌呤醇不良反应[J].中国误诊学杂志,2004,4(6):947.
[14]黄玉斌.381例别嘌醇不良反应分析[J].中国药物应用与监测,2005,2(1):32-34.
[15]傅得兴.别嘌醇的不良反应及安全应用[J].药物不良反应杂志,2003,5(3):173-176.
[16]蔡泳,陈雪观.别嘌醇致严重不良反应分析[J].医药导报,2012,31(2):264-266.
[17]李新强,王丽英.中医药治疗高尿酸血症的研究进展[J].中国实验方剂学杂志,2011,17(3):226-228.
[18]朱春胜,张冰,林志健,等.中医药治疗高尿酸血症的研究进展[J].中华中医药杂志,2015,12(6):4374-4376.
[19]焦剑.中医药治疗高尿酸血症的研究进展[J].天津中医药,2014,31(6):379-381.
[20]张宸,李君玲,田佳星,等.高尿酸血症的中医药治疗研究进展[J].中国新药杂志,2013,22(6):670-673.
[21]李琳,张敏,李苒,等.中药治疗高尿酸血症实验研究进展[J].天津中医药,2013,30(3):190-192.
[22]李莉,田甜,应森林.痛风性关节炎的中医药治疗进展[J].天津中医药大学学报,2013,32(4):253-255.
[23]徐晨,刘舒,刘志强,等.离心超滤质谱法筛选中药复方二妙丸中黄嘌呤氧化酶抑制剂[J].高等学校化学学报,2014,35(8):1640-1645.
[24]唐诗韵,万雪梅,贾琴,等.二妙散系列方治疗痛风的系统评价[J].中药药理与临床,2014,30(6):198-202.
[25]陈维佳,武毅,徐晨,等.紫外可见光谱及成像方法研究二妙丸药物对高尿酸血症疗效的影响[J].光谱学与光谱分析,2015,35(4):956-960.
[26]吕耀中,胡庆华,王星,等.二妙丸水提取物对高尿酸血症小鼠尿酸失衡及其相关基因和蛋白水平的影响[J].中草药,2010,41(3):418-423.
[27]熊湘明,田凤石,姜霞,等.二妙散加减方对实验性高尿酸血症肾损害的保护作用[J].天津医科大学学报,2007,13(1):90-92.
[28]王晗,张敏,路腾飞,等.高尿酸血症动物模型研究进展[J].天津中医药大学学报,2014,33(4):253-256.
[29]孟笑玮,樊克涛,代向东,等.高尿酸血症动物模型的实验研究[J].天津中医药,2015,32(10):614-617.
[30]刘淑芬,曾学军.高尿酸血症动物模型研究进展[J].基础医学与临床,2011,31(3):344-347.
[31]马思佳,霍娇,张立实.高尿酸血症动物模型研究进展[J].卫生研究,2015,44(1):158-162.
[32]彭仙娥,黄之敏,黄萌,等.高尿酸血症与代谢综合征关系[J].中国公共卫生,2009,25(9):1088-1089.
[33]李京.高尿酸血症与代谢综合征关系的研究[D].潍坊:潍坊医学院,2014.
[34]Akkasilpa S,Avihingsanon Y,Hanvivadhanakul P,et al.Clinicalmani-festations of patients with hyperuricemia[J].Journal of the Medical Association of Thailand,2004,87(Suppl2):S41.
[35]Keiiehi S,Shinichi K,Yuji I,et al.Determination of atractylon in Atraetylodes rhizome using supercritieal fluid ehromatography 011-line coupled with supereritical fluid extraction by the direct induefion method[J].Journal of Chromatography A,1998,810(1-2):252.