中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
3期
380-385
,共6页
潘红英%时乐%徐立%尹莲%曾宛平%张光际%杨凡
潘紅英%時樂%徐立%尹蓮%曾宛平%張光際%楊凡
반홍영%시악%서립%윤련%증완평%장광제%양범
加味四妙方%中草药提取物%高尿酸血症%黄嘌呤氧化酶%嘌呤核苷磷酸化酶%尿酸酶
加味四妙方%中草藥提取物%高尿痠血癥%黃嘌呤氧化酶%嘌呤覈苷燐痠化酶%尿痠酶
가미사묘방%중초약제취물%고뇨산혈증%황표령양화매%표령핵감린산화매%뇨산매
modified Simiaowan%plant extracts,Chinese%hyperurice mia%xanthine oxidase%purine nucleoside phosphorylase%uricase
目的:探讨加味四妙丸(MSW)有效部位群(EFC)对高尿酸血症大鼠血清尿酸水平的影响及其作用机制。方法采用由次黄嘌呤和尿酸酶抑制剂氧嗪酸钾制备持续性大鼠高尿酸血症模型,记录每日摄食量,收集末次造模后12 h尿液,ig给予模型大鼠MSW 50 g·kg -1以及EFC 12.5,25和50 g·kg -1,连续5 d;采用尿酸排泄抑制剂烟酸制备高尿酸血症模型,ig 给予模型大鼠 MSW 50 g·kg -1以及 EFC 50 g·kg -1,连续3 d。末次给药后,取血和肝组织。全自动生化仪检测大鼠血清和尿液中尿酸水平,酶比色法测定血清、肝组织中黄嘌呤氧化酶(XOD)、分光光度法检测红细胞、肝组织中嘌呤核苷磷酸化酶(PNP)和尿酸酶等活性。结果与正常对照组相比,2种高尿酸血症模型大鼠血清尿酸水平均明显升高(P<0.01),MSW和EFC 50 g·kg -1均可显著降低2种模型大鼠血尿酸水平(P<0.01)。EFC 12.5和25 g·kg -1可降低由氧嗪酸钾制备的持续性高尿酸血症大鼠血尿酸水平(P<0.05),MSW和EFC各剂量组均可明显升高模型动物红细胞PNP活性(P<0.01),EFC 25和50 g·kg -1还可显著降低血清XOD 活性(P<0.05,P<0.01)。对由烟酸复制的大鼠高尿酸血症模型,MSW 50 g·kg -1和EFC 50 g·kg -1均能升高肝组织尿酸酶活性(P<0.05),EFC 50g·kg-1能显著降低模型大鼠血清中XOD活性(P<0.01)。结论 EFC能降低高尿酸血症模型大鼠的尿酸水平,其机制可能与其抑制血清XOD活性使尿酸合成减少以及激活尿酸酶活性促进尿酸分解有关。
目的:探討加味四妙汍(MSW)有效部位群(EFC)對高尿痠血癥大鼠血清尿痠水平的影響及其作用機製。方法採用由次黃嘌呤和尿痠酶抑製劑氧嗪痠鉀製備持續性大鼠高尿痠血癥模型,記錄每日攝食量,收集末次造模後12 h尿液,ig給予模型大鼠MSW 50 g·kg -1以及EFC 12.5,25和50 g·kg -1,連續5 d;採用尿痠排洩抑製劑煙痠製備高尿痠血癥模型,ig 給予模型大鼠 MSW 50 g·kg -1以及 EFC 50 g·kg -1,連續3 d。末次給藥後,取血和肝組織。全自動生化儀檢測大鼠血清和尿液中尿痠水平,酶比色法測定血清、肝組織中黃嘌呤氧化酶(XOD)、分光光度法檢測紅細胞、肝組織中嘌呤覈苷燐痠化酶(PNP)和尿痠酶等活性。結果與正常對照組相比,2種高尿痠血癥模型大鼠血清尿痠水平均明顯升高(P<0.01),MSW和EFC 50 g·kg -1均可顯著降低2種模型大鼠血尿痠水平(P<0.01)。EFC 12.5和25 g·kg -1可降低由氧嗪痠鉀製備的持續性高尿痠血癥大鼠血尿痠水平(P<0.05),MSW和EFC各劑量組均可明顯升高模型動物紅細胞PNP活性(P<0.01),EFC 25和50 g·kg -1還可顯著降低血清XOD 活性(P<0.05,P<0.01)。對由煙痠複製的大鼠高尿痠血癥模型,MSW 50 g·kg -1和EFC 50 g·kg -1均能升高肝組織尿痠酶活性(P<0.05),EFC 50g·kg-1能顯著降低模型大鼠血清中XOD活性(P<0.01)。結論 EFC能降低高尿痠血癥模型大鼠的尿痠水平,其機製可能與其抑製血清XOD活性使尿痠閤成減少以及激活尿痠酶活性促進尿痠分解有關。
목적:탐토가미사묘환(MSW)유효부위군(EFC)대고뇨산혈증대서혈청뇨산수평적영향급기작용궤제。방법채용유차황표령화뇨산매억제제양진산갑제비지속성대서고뇨산혈증모형,기록매일섭식량,수집말차조모후12 h뇨액,ig급여모형대서MSW 50 g·kg -1이급EFC 12.5,25화50 g·kg -1,련속5 d;채용뇨산배설억제제연산제비고뇨산혈증모형,ig 급여모형대서 MSW 50 g·kg -1이급 EFC 50 g·kg -1,련속3 d。말차급약후,취혈화간조직。전자동생화의검측대서혈청화뇨액중뇨산수평,매비색법측정혈청、간조직중황표령양화매(XOD)、분광광도법검측홍세포、간조직중표령핵감린산화매(PNP)화뇨산매등활성。결과여정상대조조상비,2충고뇨산혈증모형대서혈청뇨산수평균명현승고(P<0.01),MSW화EFC 50 g·kg -1균가현저강저2충모형대서혈뇨산수평(P<0.01)。EFC 12.5화25 g·kg -1가강저유양진산갑제비적지속성고뇨산혈증대서혈뇨산수평(P<0.05),MSW화EFC각제량조균가명현승고모형동물홍세포PNP활성(P<0.01),EFC 25화50 g·kg -1환가현저강저혈청XOD 활성(P<0.05,P<0.01)。대유연산복제적대서고뇨산혈증모형,MSW 50 g·kg -1화EFC 50 g·kg -1균능승고간조직뇨산매활성(P<0.05),EFC 50g·kg-1능현저강저모형대서혈청중XOD활성(P<0.01)。결론 EFC능강저고뇨산혈증모형대서적뇨산수평,기궤제가능여기억제혈청XOD활성사뇨산합성감소이급격활뇨산매활성촉진뇨산분해유관。
OBJECTIVE Tostudytheeffectofeffectivefractions(EFC)frommodifiedSimiaoWan (MSW)onthelevelofuricacidinhyperuricemicratsandinvestigatethemechanism.METHODS Two types of hyperurice mic models were established.A persistant hyperurice mic model was prepared by giving rats oxonic acid 200 mg·kg -1 and feeding the m with hypoxanthine.The models were ig given with modified Simiaowan (MSW)50 g·kg -1 or EFC 1 2.5,25 and 50 g·kg -1 consecutively for 5 d.The models were treated with MSW or EFC 50 g·kg -1 for 3 d.After the final treatment,the uric acid concen-trations in seru m and urine were determined by an auto matic bioche mistry analyzer.The activity of xan-thine oxidase (XOD )in the serum and liver was determined by enzymic colorimetric method.The activity of purine nucleoside phosphorylase (PNP)and uricase was detected by spectrophotometry. RESULTS Comparedwithnormalcontrolgroup,theserumlevelofuricacidinbothmodelgroupswas remarkably increased(P<0.01 ).Compared to model control group,MSW 50 g·kg -1 and EFC 12.5, 25 and 50 g·kg -1 significantly reduced the serum level of uric acid(P<0.05,P<0.01 ),but increased the activity of erythrocyte PNP(P<0.01 )in the oxonic acid potassium-induced hyperuricemia rats. MSW 50 g·kg -1 and EFC 50 g·kg -1 elevated the activity of liver uricase in the nicotinic acid-induced hyperuricemia rats(P<0.05).EFC 50 g·kg -1 also significantly decreased the serum XOD activity of hyperuricemicrats.CONCLUSION EFCsignificantlyinhibitstheserumlevelofuricacidinhyperurice-mic rats,which might involve down-regulation of protein levels of serum XOD to inhibit the production of uric acid and activation of uricase to pro mote the deco mposition of uric acid.