黃敬群,張軍勇,李偉中,張亮,高穎,李光
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槲皮素對痛風(fēng)性關(guān)節(jié)炎大鼠的治療作用及腎功能的影響
黃敬群1,張軍勇2,李偉中3,張亮1,高穎1,李光1
摘要:目的探討槲皮素對急性痛風(fēng)性關(guān)節(jié)炎大鼠的治療作用及其對腎功能的影響。方法70只雄性SD大鼠隨機均分為空白對照組,模型組,秋水仙堿組(0.5 mg/kg),別嘌醇組(20 mg/kg),槲皮素低、中、高劑量組(100、200、400 mg/kg)。連續(xù)灌胃給藥7 d,第5天采用微晶尿酸鈉和次黃嘌呤法制備大鼠急性痛風(fēng)性關(guān)節(jié)炎模型。造模前和造模后2、6、12、24和48 h用縛線法測取右后肢小腿踝關(guān)節(jié)同一部位周徑,計算腫脹率;采用比色法、酶聯(lián)免疫吸附法等測定大鼠血清中尿酸(UA),β2-微球蛋白(β2-MG),胱素C (Cys-C),尿素(Urea),肌酐(Cr)含量。脫頸處死大鼠,取腎臟稱質(zhì)量,計算腎臟指數(shù)。結(jié)果槲皮素、秋水仙堿、別嘌醇能夠顯著抑制痛風(fēng)性關(guān)節(jié)炎大鼠踝關(guān)節(jié)腫脹率;造模后8 h,秋水仙堿、槲皮素組血清UA水平均高于空白對照組和別嘌醇組,別嘌醇組低于空白對照組;48 h后,除別嘌醇組血清UA水平明顯低于其余組外,其余組間差異均無統(tǒng)計學(xué)意義。各組比較,空白對照組β2-MG、Cys-C水平最低,別嘌醇組Urea、Cr水平及腎臟指數(shù)均最高(均P<0.05)。結(jié)論槲皮素對急性痛風(fēng)性關(guān)節(jié)炎大鼠有顯著的抗炎作用,但造模可能導(dǎo)致腎功能不同程度的損害。槲皮素對輕度腎損傷未見明顯的保護作用,別嘌醇給藥后加重腎功能損傷。
關(guān)鍵詞:痛風(fēng)性關(guān)節(jié)炎;高尿酸血癥;槲皮素;秋水仙堿;別嘌醇;腎功能
痛風(fēng)性關(guān)節(jié)炎(gouty arthritis,GA)是由于血液尿酸(uric acid, UA)增高,尿酸鹽結(jié)晶(monosodium urate crystals,MSU)沉積在關(guān)節(jié)囊、滑膜、軟骨等組織,受累關(guān)節(jié)出現(xiàn)紅、腫、熱、痛,導(dǎo)致關(guān)節(jié)畸形及功能障礙[1-3]。大多數(shù)痛風(fēng)性關(guān)節(jié)炎患者存在高尿酸血癥,其被認(rèn)為是痛風(fēng)發(fā)展的一個關(guān)鍵性危險因素[4]。UA產(chǎn)生過多、腎臟UA排泄障礙或者這兩個因素的綜合作用可導(dǎo)致高尿酸血癥的發(fā)生[5-6]。痛風(fēng)性關(guān)節(jié)炎的治療一方面需要降低血清UA水平,另一方面需要控制急性炎癥發(fā)作[7]。目前治療藥物包括非甾體類抗炎藥吲哚美辛、秋水仙堿、糖皮質(zhì)激素和別嘌醇等,但其均具有嚴(yán)重的不良反應(yīng),如胃腸毒性、肝腎功能損害和胃腸道出血等[8-9]。因此,從天然產(chǎn)物中尋求安全有效的成分治療痛風(fēng)性關(guān)節(jié)炎是未來的研究熱點。黃酮類化合物槲皮素廣泛存在于茶葉、洋蔥、西蘭花、蘋果、桃子、蕎麥等幾乎所有的植物性食物中,具有抗菌、抗病毒、抗氧化、抗炎和誘導(dǎo)變異細(xì)胞凋亡等生物活性[10-11]。本課題組前期研究發(fā)現(xiàn),槲皮素不能夠降低正常和高尿酸血癥小鼠血清UA水平[12],但能夠顯著抑制痛風(fēng)性關(guān)節(jié)炎大鼠踝關(guān)節(jié)腫脹度和炎癥因子含量,提高機體抗氧化酶活性,通過抗炎和抗氧化作用發(fā)揮治療痛風(fēng)性關(guān)節(jié)炎功效[13]。高尿酸血癥和痛風(fēng)性關(guān)節(jié)炎可能影響到腎臟,尿酸鹽不僅沉積在關(guān)節(jié)滑膜組織,還會沉積在腎實質(zhì)中,導(dǎo)致腎功能不全[14]。本研究采用微晶尿酸鈉和次黃嘌呤法[15-16]建立大鼠急性痛風(fēng)性關(guān)節(jié)炎模型,探討槲皮素對急性痛風(fēng)性關(guān)節(jié)炎大鼠的治療作用并觀察其對腎功能的影響,為槲皮素的進一步研發(fā)提供實驗依據(jù)。
1.1材料
1.1.1動物雄性SD大鼠70只,體質(zhì)量(200±20)g,清潔級,購自軍事醫(yī)學(xué)科學(xué)院實驗動物中心,許可證編號:SCXK-2012-0004。分籠飼養(yǎng),自由飲水、進食,溫度(25±2)℃,通風(fēng)良好,自然光照。
1.1.2藥物與試劑秋水仙堿片(西雙版納版納藥業(yè)有限責(zé)任公司,0.5 mg/片,批號:130505);別嘌醇片[世貿(mào)天階制藥(江蘇)有限責(zé)任公司,0.1 g/片,批號:20140610]。槲皮素(上海將來實業(yè)有限公司,純度98%,批號:A007353-50g);微晶尿酸鈉(批號:U2875-5G)、次黃嘌呤(批號:H9377-5G)均購自Sigma公司。UA試劑盒:柏定生物工程(北京)有限公司,尿酸酶比色法。尿素(Urea)試劑盒:柏定生物工程(北京)有限公司,尿酶-谷氨酸脫氫酶法。β2-微球蛋白(β2-microglob?ulin,β2-MG)試劑盒、胱素C (Cystatin C, Cys-C)試劑盒:羅氏診斷產(chǎn)品上海有限公司,ELISA法。肌酐(Creatinine, Cr)試劑盒:北京九強生物技術(shù)股份有限公司,肌氨酸氧化酶法。
1.1.3儀器FA1104型電子天平(上海精科天平有限公司);日立7600-020全自動生化分析儀(日立公司);Thermo Scientific Multiskan Go全波長酶標(biāo)儀(Thermo go公司)。
1.2動物分組70只SD大鼠適應(yīng)性喂養(yǎng)1周后,采用隨機數(shù)字表法分為空白對照組,模型組,秋水仙堿組(0.5 mg/kg),別嘌醇組(20 mg/kg),槲皮素低、中、高劑量組(100、200、400 mg/kg),每組10只。
1.3溶液制備
1.3.1秋水仙堿混懸液的制備將秋水仙堿片20片放入研缽內(nèi)研成細(xì)末,溶解于200 mL蒸餾水中,充分混勻,制備成濃度為0.05 g/L的秋水仙堿混懸液。
1.3.2別嘌醇混懸液的制備將別嘌醇片4片放入研缽內(nèi)研成細(xì)末,溶解于200 mL蒸餾水中,制備成濃度為2 g/L的別嘌醇混懸液。
1.3.3槲皮素混懸液的制備分別精密稱取槲皮素2.0、4.0 和8.0 g,放入研缽內(nèi)研成細(xì)末,溶解于200 mL蒸餾水中,制備成濃度為10、20和40 g/L的槲皮素混懸液。
1.3.4尿酸鈉混懸液的制備精密稱取尿酸鈉結(jié)晶400 mg,放入研缽內(nèi)研成極細(xì)粉末,加入10 mL生理鹽水,充分混勻,制備成濃度為40 g/L的尿酸鈉混懸液。
1.3.5次黃嘌呤混懸液的制備精密稱取次黃嘌呤粉末8.0 g,溶解于160 mL生理鹽水中,制備成濃度為50 g/L的次黃嘌呤混懸液。
1.4給藥方法以每100 g大鼠體質(zhì)量灌胃1 mL為標(biāo)準(zhǔn),空白對照組和模型組分別灌胃蒸餾水;陽性藥對照組分別灌胃秋水仙堿和別嘌醇混懸液,槲皮素低、中、高劑量組分別灌胃對應(yīng)濃度槲皮素混懸液。每日1次,連續(xù)7 d,第5天給藥1 h后造模。
1.5造模方法空白對照組腹腔注射1 mL/100 g生理鹽水,模型組、秋水仙堿組、別嘌醇組和槲皮素低、中、高劑量組分別按1 mL/100 g(500 mg/kg)腹腔注射次黃嘌呤混懸液。腹腔注射完畢后大鼠乙醚麻醉,模型組、秋水仙堿組、別嘌醇組和槲皮素低、中、高劑量組大鼠用75%乙醇消毒右后肢小腿踝關(guān)節(jié),用6號注射針在大鼠右后踝關(guān)節(jié)背側(cè)45°方向插入至脛骨肌腱內(nèi)側(cè),感覺有落空感后將充分混勻的0.1 mL尿酸鈉混懸液注入到關(guān)節(jié)腔內(nèi),緩慢拔出針頭,防止尿酸鈉混懸液漏出??瞻讓φ战M右后肢小腿踝關(guān)節(jié)注射等體積生理鹽水。
1.6檢測指標(biāo)
1.6.1大鼠踝關(guān)節(jié)腫脹率造模前和造模后2、6、12、24、48 h用縛線法測量大鼠右后肢踝關(guān)節(jié)同一部位周徑,計算腫脹率。腫脹率=(致炎后踝關(guān)節(jié)周徑-致炎前踝關(guān)節(jié)周徑)/致炎前踝關(guān)節(jié)周徑×100%。
1.6.2血清UA、Urea、Cr、β2-MG和Cys-C水平測定造模后8 h用玻璃毛細(xì)管從各大鼠眼底靜脈叢取血1.5 mL,室溫下放置1 h后4 000 r/min離心10 min,取上清,7600-020全自動生化分析儀測定血清UA水平。第7天給藥后1 h大鼠乙醚麻醉,腹主靜脈取血5.0 mL,室溫下放置1 h后4 000 r/min離心10 min,取上清,放入-80℃冰箱待測。分別用7600-020全自動生化分析儀和Thermo go全自動酶標(biāo)儀測定血清中UA、Urea、Cr、β2-MG和Cys-C水平。
1.6.3臟器指數(shù)測定大鼠腹主靜脈取血后脫頸處死,取腎臟稱質(zhì)量,計算腎臟指數(shù)。腎臟指數(shù)=腎臟質(zhì)量/體質(zhì)量× 100%。
1.6.4組織病理學(xué)檢查取大鼠腎臟組織,10%中性福爾馬林溶液中固定,梯度乙醇脫水,透明,常規(guī)石蠟包埋切片,HE染色,光鏡下觀察組織病理形態(tài)學(xué)改變。
1.7統(tǒng)計學(xué)方法采用SPSS 19.0統(tǒng)計軟件進行數(shù)據(jù)分析。計量資料用±s表示,不同時間點多組間比較采用單因素方差分析,進一步組間多重比較采用LSD-t檢驗,2組間比較采用獨立樣本t檢驗,P < 0.05為差異有統(tǒng)計學(xué)意義。
2.1槲皮素對大鼠踝關(guān)節(jié)腫脹率的影響尿酸鈉誘導(dǎo)的急性痛風(fēng)性關(guān)節(jié)炎大鼠踝關(guān)節(jié)腫脹率在造模后均明顯增加(均P<0.05),說明造模成功。各造模組大鼠在48 h后腫脹開始明顯減輕,說明此模型適用于痛風(fēng)性關(guān)節(jié)炎的急性期。秋水仙堿組,別嘌醇組,槲皮素低、中、高劑量組在2~48 h與模型組比較,踝關(guān)節(jié)腫脹率均顯著降低(均P < 0.05);槲皮素低、中、高劑量組量效關(guān)系不顯著(均P>0.05),見圖1。
Fig. 1 Comparison of ankle joint swelling rates at different time points between seven groups圖1 各組大鼠造模后不同時間點踝關(guān)節(jié)腫脹率比較
2.2槲皮素對大鼠血清UA水平的影響造模后8 h,模型組大鼠血清UA水平顯著高于空白對照組,表明大鼠腹腔注射次黃嘌呤500 mg/kg成功誘導(dǎo)出高尿酸血癥模型;秋水仙堿組,槲皮素低、中、高劑量組血清UA水平均明顯高于空白對照組和別嘌醇組,別嘌醇組低于空白對照組(均P<0.05);模型組,秋水仙堿組,槲皮素低、中、高劑量組間多重比較差異均無統(tǒng)計學(xué)意義。48 h后,除別嘌醇組血清UA水平明顯低于其余組外,其余組間差異均無統(tǒng)計學(xué)意義。見表1。
Tab. 1 Comparison of serum uraic acid levels of rat at different time points between seven groups表1 各組間不同時間點大鼠血清UA水平的比較(n=10,μmol/L,±s)
Tab. 1 Comparison of serum uraic acid levels of rat at different time points between seven groups表1 各組間不同時間點大鼠血清UA水平的比較(n=10,μmol/L,±s)
*P < 0.05;a與空白對照組比較,b與模型組比較,c與秋水仙堿組比較,d與別嘌醇組比較,P < 0.05
組別空白對照組模型組秋水仙堿組別嘌醇組槲皮素低劑量組槲皮素中劑量組槲皮素高劑量組F 8 h UA 184.40±46.66 349.90±49.72a339.90±50.46a83.20±15.92abc322.50±53.47ad325.20±44.38ad322.80±37.54ad52.750*48 h UA 144.50±19.54 150.40±40.09 149.00±25.10 18.90±3.14abc135.50±22.87d148.50±42.77d150.80±29.33d28.809*
2.3槲皮素對大鼠β2-MG、Cys-C、Urea和Cr水平的影響模型組,秋水仙堿組,別嘌醇組,槲皮素低、中、高劑量組β2-MG、Cys-C水平均高于空白對照組(均P<0.05);空白對照組,模型組,秋水仙堿組,槲皮素低、中、高劑量組Urea、Cr水平均明顯低于別嘌醇組(均P<0.05);其余組間差異均無統(tǒng)計學(xué)意義。見表2。
Tab. 2 Comparison of serum levels of β2-MG, Cys-C, Urea, and Cr in rats between seven groups表2 各組大鼠血清β2-MG、Cys-C、Urea和Cr水平比較(n=10,±s)
Tab. 2 Comparison of serum levels of β2-MG, Cys-C, Urea, and Cr in rats between seven groups表2 各組大鼠血清β2-MG、Cys-C、Urea和Cr水平比較(n=10,±s)
*P < 0.05;a與空白對照組比較,b與模型組比較,c與秋水仙堿組比較,d與別嘌醇組比較,P < 0.05
組別空白對照組模型組秋水仙堿組別嘌醇組槲皮素低劑量組槲皮素中劑量組槲皮素高劑量組F β2-MG (mg/L) 27.32±7.19 36.27±2.08a35.96±2.66a35.42±5.22a32.95±3.50a31.80±3.30a32.81±5.21a4.882*Cys-C (μg/L) 14.88±3.04 21.17±2.91a20.09±3.15a20.92±0.82a18.28±2.95a18.47±2.47a21.05±1.49a8.001*Urea (mmol/L) 7.60±0.96 6.44±0.74 5.95±0.35 57.60±7.39abc6.70±0.91d6.66±0.77d6.49±1.18d440.278*Cr (μmol/L) 19.20±1.81 22.20±2.66 23.30±1.77 287.60±35.96abc21.70±1.77d21.80±2.10d20.90±1.85d537.523*
2.4槲皮素對大鼠腎臟指數(shù)的影響別嘌醇組腎臟指數(shù)(0.78±0.04)%均明顯高于空白對照組(0.35± 0.03)%,模型組(0.33±0.03)%,秋水仙堿組(0.36± 0.05)%,槲皮素低(0.34±0.02)%、中(0.36±0.03)%、高劑量組(0.35±0.01)%,差異有統(tǒng)計學(xué)意義(F= 248.227,P<0.05)。
2.5病理組織形態(tài)學(xué)結(jié)果空白對照組,模型組,秋水仙堿組,槲皮素低、中、高劑量組大鼠腎外觀及切面正常,別嘌醇組大鼠各腎外觀均水腫明顯,被膜緊張??瞻讓φ战M鏡檢可見腎小管、腎小球結(jié)構(gòu)清楚,無明顯改變;模型組,秋水仙堿組,槲皮素低、中、高劑量組腎小球及近端腎小管組織結(jié)構(gòu)清楚,形態(tài)和染色基本正常,個別區(qū)域腎小管上皮細(xì)胞輕度水腫,毛細(xì)血管輕度擴張充血。別嘌醇組可見廣泛的小血管及靜脈嚴(yán)重充血,腎小球體積輕度增大,球囊粘連,系膜細(xì)胞增生,系膜基質(zhì)增寬,腎小管間質(zhì)毛細(xì)血管擴張充血,上皮細(xì)胞空泡變性,見圖2。
痛風(fēng)性關(guān)節(jié)炎的發(fā)病機制是高尿酸血癥伴隨著尿酸鹽結(jié)晶在關(guān)節(jié)及其周圍組織沉積,噬中性粒細(xì)胞滲出,產(chǎn)生紅、腫、熱、痛[17]。對痛風(fēng)來說,兩個重要的治療目標(biāo)是減輕炎癥反應(yīng)和降低血清的UA水平[18-19]。文獻報道,注射尿酸鈉結(jié)晶16~24 h后大鼠踝關(guān)節(jié)關(guān)節(jié)液中噬中性粒細(xì)胞大量聚集,同時滑膜表面和襯里有大量白細(xì)胞滲入[20]。本研究采用大鼠腹腔內(nèi)注射次黃嘌呤誘導(dǎo)產(chǎn)生高尿酸血癥,同時將尿酸鈉晶體注入大鼠踝關(guān)節(jié)腔內(nèi)造成急性痛風(fēng)性關(guān)節(jié)炎病變模型,該模型符合臨床急性痛風(fēng)性關(guān)節(jié)炎的發(fā)生機制。結(jié)果顯示,大鼠造模后2 h開始出現(xiàn)踝關(guān)節(jié)腫脹,24 h達到高峰,48 h后癥狀開始緩解。與模型組比較,秋水仙堿組,別嘌醇組,槲皮素低、中、高劑量組能夠顯著抑制痛風(fēng)性關(guān)節(jié)炎大鼠踝關(guān)節(jié)腫脹率,提示這3種藥給藥后均能夠顯著減少模型大鼠關(guān)節(jié)腔內(nèi)關(guān)節(jié)液的容積,減輕炎癥反應(yīng)。
本研究顯示,造模后8 h,模型組,秋水仙堿組,槲皮素低、中、高劑量組大鼠血清UA水平均顯著高于空白對照組;48 h后,其血清UA水平均降低到正常范圍;而別嘌醇組的血清UA水平在8 h和48 h時均明顯低于其他各組,提示應(yīng)用此模型觀察大鼠血清UA水平時,應(yīng)該在8 h左右取血測定比較合適;48 h時別嘌醇仍能夠顯著降低高尿酸血癥大鼠血清UA水平,而槲皮素和秋水仙堿對高尿酸血癥大鼠血清UA水平無明顯影響,與以往文獻報道一致[12,15,21]。
多項流行病學(xué)、臨床及基礎(chǔ)實驗研究表明,UA的升高可以直接使腎小球入球小動脈發(fā)生微血管病變[22-23]。黃嘌呤氧化酶抑制劑別嘌醇臨床廣泛用于抑制UA合成,但口服該藥會加重肝腎功能不全患者的腎臟負(fù)擔(dān),有報道稱可引起藥源性急性腎衰和肝壞死[24]。微管解聚劑秋水仙堿可通過抑制多形核白細(xì)胞的活性和運動產(chǎn)生抗炎作用[25-26],目前主要用于治療痛風(fēng)性關(guān)節(jié)炎的急性發(fā)作,但同時具有比較嚴(yán)重的毒性反應(yīng),如胃腸道反應(yīng)、骨髓毒性反應(yīng)、肝腎功能損害、精神抑郁等,藥物過量甚至可導(dǎo)致死亡[27]。臨床常用內(nèi)源性標(biāo)志物β2-MG、Cys-C、Urea 和Cr等評價腎臟功能。β2-MG是一種體內(nèi)有核細(xì)胞產(chǎn)生的小分子循環(huán)蛋白質(zhì),腎小球濾過后,99.9% 的β2-MG在近端腎小管被重吸收,在腎小管細(xì)胞的溶酶體中降解,最后經(jīng)尿排出[28]。Cys-C是一種反映腎小球濾過膜通透性早期變化的理想的內(nèi)源性標(biāo)志物,可以在腎小球濾過率輕微降低時升高,有較強的敏感性[29]。血清β2-MG和Cys-C的升高可靈敏地反映早期腎小球濾過率的降低。本研究顯示,模型組,秋水仙堿組,別嘌醇組,槲皮素低、中、高劑量組β2-MG、Cys-C水平均高于空白對照組,這可能是與高尿酸血癥有關(guān)的腎損傷的早期表現(xiàn),而秋水仙堿和槲皮素并沒有明顯降低β2-MG和Cys-C水平而表現(xiàn)出對腎損傷的保護作用。
Urea和Cr也是反映腎臟功能損傷的實驗室指標(biāo)之一[30],但是對腎小球濾過率的診斷不夠靈敏,在腎功能損害早期,血Urea和Cr可在正常范圍,只有當(dāng)腎小球濾過率下降至正常的50%以上時,Urea和Cr開始迅速上升,因此當(dāng)Urea和Cr明顯高于正常時,常表示腎功能已嚴(yán)重?fù)p害。本研究中別嘌醇組血清Urea和Cr水平均明顯高于空白對照組,而且腎臟指數(shù)顯著升高,組織病理學(xué)檢查結(jié)果也可見別嘌醇給藥后造成一定程度的腎功能損傷。
綜上所述,槲皮素、秋水仙堿、別嘌醇對急性痛風(fēng)性關(guān)節(jié)炎大鼠有顯著的抗炎作用。微晶尿酸鈉和次黃嘌呤法制備的大鼠急性痛風(fēng)性關(guān)節(jié)炎模型可能導(dǎo)致腎功能不同程度的損害,槲皮素對輕度腎損傷未見明顯的保護作用,給予別嘌醇后會加重腎損傷。
(圖2見插頁)
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(2015-03-01收稿2015-09-16修回)
(本文編輯陳麗潔)
作者單位:1中國人民解放軍第252醫(yī)院制劑中心(郵編071000),2院部,3檢驗科
The therapeutic effect of quercetin on gouty arthritis and its influence in renal function in rats
HUANG Jingqun1, ZHANG Junyong2, LI Weizhong3, ZHANG Liang1, GAO Ying1, LI Guang1
1 Center of Praeparatum, 2 Command Institution, 3 Department of Laboratory Medicine, NO. 252 Hospital of PLA, Baoding,
Hebei 071000, China
Abstract:Objective To investigate the therapeutic effect of quercetin on acute gouty arthritis and its influence in re?nal function in rats. Methods Seventy male Sprague-Dawley rats were randomly divided into normal control group, model group, colchicine group (0.5 mg/kg), allopurinol group (20 mg/kg), quercetin 100, 200 and 400 mg/kg groups (n=10 for each group). Rats were administered various drugs by oral gavage once a day for seven consecutive days throughout the experi?ment. On the fifth day, the animal model of acute arthritis was set up by giving monosodium urate crystal combined with hypo?xanthine. The inflammatory reaction was detected by measuring the circumference of right hind leg anklejoint with a tie line method at 0, 2, 6, 12, 24 and 48 h. The swelling ratio was calculated. The serum levels of uric acid (UA),β2-microglobulin (β2-MG), cystatin C (Cys-C), urea nitrogen (Urea) and creatinine (Cr) were detected by colorimetry and enzyme-linked im?munosorbent assay.Rats were sacrificed at the end of experiment, and the kidney was weighed and the renal index was calcu?lated. Results Treatment with quercetin, colchicine or allopurinol can significantly attenuate swelling rate in rats of acute gouty arthritis. The serum levels of UA were significantly higher in colchicine group and quercetin group than those of nor?mal control group and allopurinol group. The serum levels of UA was significantly lower in allopurinol group than that of nor?mal control group. After 48-h modeling, there was no significant difference in serum UA level between seven groups except allopurinol group. The levels of β2-MG and Cys-C were the lowest in normal control group than those of other groups. The se?rum levels of Urea and Cr and renal index were the highest in allopurinol group compared with those of other groups (P < 0.05). ConclusionQuercetin shows a significant effect of anti-inflammatory on acute gouty arthritis in rats. The model es?tablishment may lead to different degrees of renal damage. Quercetin has no protective effect against renal injury, and allopu?rinol aggravates kidney injury.
Key words:gouty arthritis; hyperuricemia; quercetin; colchicines; allopurinol; renal function
中圖分類號:R965.3
文獻標(biāo)志碼:A
DOI:10.11958/58360
基金項目:中國博士后科學(xué)基金項目(2012M512105)
作者簡介:黃敬群(1970),男,主管藥師,博士,主要從事中藥藥理研究