中华泌尿外科杂志
中華泌尿外科雜誌
중화비뇨외과잡지
CHINESE JOURNAL OF UROLOGY
2012年
1期
32-36
,共5页
目的 探讨三聚氰胺( melamine,Mel)诱导大鼠肾脏损伤的机制. 方法 雄性SD大鼠48只随机分为4组,每组12只.A组为空白对照组,喂标准颗粒饲料和饮用自来水；B组为结石诱导组,喂含3％ Mel的颗粒饲料和饮用自来水；C组喂食含3％ Mel的颗粒饲料和饮用含2％牛磺酸的水；D组喂标准颗粒饲料和饮用含2％牛磺酸的水.共喂养3个月.每周收集大鼠24 h尿液检测pH、肌酐、尿酸、蛋白、8-IP、H2O2和Mel水平.第3个月末处死全部大鼠,采血检测肌酐,进行肾脏病理分析(HE和Oil Red O染色)及线粒体分离和检测. 结果 A组和D组尿液中未检测出Mel,B组和C组第1～4周尿液中Mel浓度分别为(3.16±0.45)、(4.39±0.21)、(5.40±0.28)、(5.50±3.26) mg/ml和(3.52±0.49)、(4.32 ±0.13)、(5.34±0.40)、(5.46±2.99) mg/ml,与A组比较,B组和C组尿液Mel浓度有药物暴露时间依赖性.A组尿蛋白、尿肌酐、肌酐清除率、肾脏/体质量比值分别为(6.45±1.45)mg/24 h、(28.0±7.4) mmol/L、(0.56±0.03)ml·min-1·100g-1、(2.29 ±0.89) mg/g,B组和C组分别为(14.56±7.69) mg/24 h、(56.8±5.2) mmol/L、(0.29±0.05)ml· min-1· 100g-1、(4.16±0.27) mg/g和(16.44±6.29) mg/24 h、(55.8±7.4) mmol/L、(0.30±0.07)ml·min-1·100g-1、(4.40±0.56)mg/g,与A组比较,B组和C组尿蛋白显著增多,尿肌酐减少,肌酐清除率降低,肾脏/体质量比值增加.与B组比较,C组肾功能无明显变化,血清肌酐,尿蛋白降低不明显,差异无统计学意义(P＞0.05).B组和C组尿H2O2、8-IP及线粒体氧化检测试剂SOD、GSH-PX值分别为(28.5±5.2) mmol/L、( 3.26±1.6) pg/ml、(21.1±7.8)U/mg prot、(19.0±2.5)活力单位和(26.7±4.8) mmol/L、(2.99±8.5)pg/ml、(20.3±6.9) U/mg prot、(17.9±4.8)活力单位,B组和C组比较差异无统计学意义(P＞0.05).病理分析可见Mel晶体主要集中在肾小管腔内(B组和C组),肾脏间质损伤明显,并随着药物暴露时间的增加肾脏炎症和纤维化进行性发展.结论 Mel可诱导大鼠肾脏损害和结石形成,结石主要集中在内髓区肾小管位置,Mel不是通过氧化应激途径致肾脏损伤的.
目的 探討三聚氰胺( melamine,Mel)誘導大鼠腎髒損傷的機製. 方法 雄性SD大鼠48隻隨機分為4組,每組12隻.A組為空白對照組,餵標準顆粒飼料和飲用自來水；B組為結石誘導組,餵含3％ Mel的顆粒飼料和飲用自來水；C組餵食含3％ Mel的顆粒飼料和飲用含2％牛磺痠的水；D組餵標準顆粒飼料和飲用含2％牛磺痠的水.共餵養3箇月.每週收集大鼠24 h尿液檢測pH、肌酐、尿痠、蛋白、8-IP、H2O2和Mel水平.第3箇月末處死全部大鼠,採血檢測肌酐,進行腎髒病理分析(HE和Oil Red O染色)及線粒體分離和檢測. 結果 A組和D組尿液中未檢測齣Mel,B組和C組第1～4週尿液中Mel濃度分彆為(3.16±0.45)、(4.39±0.21)、(5.40±0.28)、(5.50±3.26) mg/ml和(3.52±0.49)、(4.32 ±0.13)、(5.34±0.40)、(5.46±2.99) mg/ml,與A組比較,B組和C組尿液Mel濃度有藥物暴露時間依賴性.A組尿蛋白、尿肌酐、肌酐清除率、腎髒/體質量比值分彆為(6.45±1.45)mg/24 h、(28.0±7.4) mmol/L、(0.56±0.03)ml·min-1·100g-1、(2.29 ±0.89) mg/g,B組和C組分彆為(14.56±7.69) mg/24 h、(56.8±5.2) mmol/L、(0.29±0.05)ml· min-1· 100g-1、(4.16±0.27) mg/g和(16.44±6.29) mg/24 h、(55.8±7.4) mmol/L、(0.30±0.07)ml·min-1·100g-1、(4.40±0.56)mg/g,與A組比較,B組和C組尿蛋白顯著增多,尿肌酐減少,肌酐清除率降低,腎髒/體質量比值增加.與B組比較,C組腎功能無明顯變化,血清肌酐,尿蛋白降低不明顯,差異無統計學意義(P＞0.05).B組和C組尿H2O2、8-IP及線粒體氧化檢測試劑SOD、GSH-PX值分彆為(28.5±5.2) mmol/L、( 3.26±1.6) pg/ml、(21.1±7.8)U/mg prot、(19.0±2.5)活力單位和(26.7±4.8) mmol/L、(2.99±8.5)pg/ml、(20.3±6.9) U/mg prot、(17.9±4.8)活力單位,B組和C組比較差異無統計學意義(P＞0.05).病理分析可見Mel晶體主要集中在腎小管腔內(B組和C組),腎髒間質損傷明顯,併隨著藥物暴露時間的增加腎髒炎癥和纖維化進行性髮展.結論 Mel可誘導大鼠腎髒損害和結石形成,結石主要集中在內髓區腎小管位置,Mel不是通過氧化應激途徑緻腎髒損傷的.
목적 탐토삼취청알( melamine,Mel)유도대서신장손상적궤제. 방법 웅성SD대서48지수궤분위4조,매조12지.A조위공백대조조,위표준과립사료화음용자래수；B조위결석유도조,위함3％ Mel적과립사료화음용자래수；C조위식함3％ Mel적과립사료화음용함2％우광산적수；D조위표준과립사료화음용함2％우광산적수.공위양3개월.매주수집대서24 h뇨액검측pH、기항、뇨산、단백、8-IP、H2O2화Mel수평.제3개월말처사전부대서,채혈검측기항,진행신장병리분석(HE화Oil Red O염색)급선립체분리화검측. 결과 A조화D조뇨액중미검측출Mel,B조화C조제1～4주뇨액중Mel농도분별위(3.16±0.45)、(4.39±0.21)、(5.40±0.28)、(5.50±3.26) mg/ml화(3.52±0.49)、(4.32 ±0.13)、(5.34±0.40)、(5.46±2.99) mg/ml,여A조비교,B조화C조뇨액Mel농도유약물폭로시간의뢰성.A조뇨단백、뇨기항、기항청제솔、신장/체질량비치분별위(6.45±1.45)mg/24 h、(28.0±7.4) mmol/L、(0.56±0.03)ml·min-1·100g-1、(2.29 ±0.89) mg/g,B조화C조분별위(14.56±7.69) mg/24 h、(56.8±5.2) mmol/L、(0.29±0.05)ml· min-1· 100g-1、(4.16±0.27) mg/g화(16.44±6.29) mg/24 h、(55.8±7.4) mmol/L、(0.30±0.07)ml·min-1·100g-1、(4.40±0.56)mg/g,여A조비교,B조화C조뇨단백현저증다,뇨기항감소,기항청제솔강저,신장/체질량비치증가.여B조비교,C조신공능무명현변화,혈청기항,뇨단백강저불명현,차이무통계학의의(P＞0.05).B조화C조뇨H2O2、8-IP급선립체양화검측시제SOD、GSH-PX치분별위(28.5±5.2) mmol/L、( 3.26±1.6) pg/ml、(21.1±7.8)U/mg prot、(19.0±2.5)활력단위화(26.7±4.8) mmol/L、(2.99±8.5)pg/ml、(20.3±6.9) U/mg prot、(17.9±4.8)활력단위,B조화C조비교차이무통계학의의(P＞0.05).병리분석가견Mel정체주요집중재신소관강내(B조화C조),신장간질손상명현,병수착약물폭로시간적증가신장염증화섬유화진행성발전.결론 Mel가유도대서신장손해화결석형성,결석주요집중재내수구신소관위치,Mel불시통과양화응격도경치신장손상적.
Objective To investigate the mechanism of melamine-induced renal damage in rats.Methods 48 male SD rats were randomly divided into 4 groups with 12 in each group and feed for 3 months.Group A were the control group,feed with standard granule feedstuff and drinking tap water.Group B were stone-induced group,feed with granule feedstuff containing 3％ Mel and drinking tap water.Group C were feed with granule feedstuff containing 3％ Mel and drinking water containing 2％ taurine.Group D were feed with standard granule feedstuff and drinking water containing 2％ taurine.Every week 24 h urine was collected to test PH,SCr,uric acid,protein,8-IP,H2O2 and Mel level.All rats were sacrificed at the end of 3 months.Blood creatinine detection,renal pathology analysis ( HE and Oil ep-red O dyeing,immunohistochemical) and mitochondria separation and detection were undertaken. Results Mel was not detedted in urine of Group A and Group D.The urine concentration of Mel in Group B and Group C in 1 week,2 weeks,3 weeks,4 weeks were 3.16 ±0.45,4.39 ±0.213,5.40 ±0.28,5.50 ±3.26 and 3.52 ±0.49,4.32 ± 0.135,5.34 ± 0.40,5.46 ± 2.99 mg/ml,respectively.Compared with Group A,the Mel concentration in urine of Group B and C were drug exposure time dependent.In Group A,the urine protein,urine creatinine clearance,serum creatinine,and renal/weight ratio were 6.45 ± 1.45 mg/24 h,28.0 ± 7.4mmol/l,0.56 ±0.03 ml · min-1 · 100g-1,2.29 ±0.89 mg/g,while in Group B and C,the urinary protein urine,serum creatinine,creatinine clearance,kidney/weight ratio were 14.56 ± 7.69,56.8 ± 5.2,0.29 ±0.05,4.16 ±0.27 and 16.44 ±6.29,55.8 ±7.4,0.30 ±0.07,4.40 ±0.56,respectively.Compared with group A,in Group B and C,the urinary protein increased significantly,urine creatinine clearance reduced,serum creatinine reduced,and renal/weight ratio increased.Compared with Group B,the improvement of renal function in Group C was not significant,and the decrease of serum creatinine and urinary protein were not obvious (P ＞ 0.05).In Group B and C,the urine H2O2,8-IP and mitochondrial oxidatie detection reagent SOD,GSH-PX numerical were 28.5 ± 5.2 mmol/1,3.26 ± 1.6 pg/ml,21.1 ± 7.8 U/mg prot,19.0 ±2.5 energy unit and 26.7 ±4.8 mmol/l,2.99 ±8.5 pg/ml,20.3 ±6.9 U/mg prot,17.9 ±4.8 energy unit,respectively.The difference between Group B and C was not statistically significant (P ＞0.05).Pathological analysis showed Mel was mainly concentrated in crystal tubular lumen (Group B and C),kidney interstitial damage was apparent,and kidney inflammation and fibrosis progressive developed with the increase of the drug exposure time. Conclusions Mel can induce kidney damage and stone formation in rats,and stone was mainly in tubular location in inner medullary zone.It is not the oxidative stress way that Mel leads to kidney damage.
