中华泌尿外科杂志
中華泌尿外科雜誌
중화비뇨외과잡지
CHINESE JOURNAL OF UROLOGY
2009年
3期
156-159
,共4页
陈业辉%钟惟德%梁颜笑%陈林强%路艳蒙%梁健健%张静%邱江%黎伟龙%谢克基%胡建波%陈立中%郑克立
陳業輝%鐘惟德%樑顏笑%陳林彊%路豔矇%樑健健%張靜%邱江%黎偉龍%謝剋基%鬍建波%陳立中%鄭剋立
진업휘%종유덕%량안소%진림강%로염몽%량건건%장정%구강%려위룡%사극기%호건파%진립중%정극립
他克莫司%肾毒性%钙离子通道阻滞剂%地尔硫草
他剋莫司%腎毒性%鈣離子通道阻滯劑%地爾硫草
타극막사%신독성%개리자통도조체제%지이류초
Tacrolimus%Nephrotoxicity%Calcium channel blocker%Diltiazem
目的 观察他克莫司(FK506)肾毒性模型中钙离子代谢的变化情况,探讨钙离子通道阻滞剂地尔硫草(Dil)对FK506肾毒性的预防作用.方法 按公式将肾移植术后FK506、环孢素(CsA)和Dil的首剂治疗剂量换算成大鼠的治疗剂量.雄性SD大鼠24只随机分成对照组、CsA组(25 mg·kg-1·d-1)、FK506组(0.8 mg·kg-1·d-1)和FK506加Dil组(0.8 mg·kg-1·d-1及8 mg·kg-1·d-1),每组6只,用药4周后建立各组大鼠肾毒性模型.观察各组大鼠SCr、血电解质、肾组织的病理改变(HE染色)、电子显微镜F肾脏细胞内超微结构的改变.结果 CsA组和FK506组大鼠SCr值分别为(36.00±2.61)和(34.17±4.54)μmol/L,均高于FK506加Dil组和对照组[(28.50±2.07)和(29.17±3.43)μmol/L,P＜0.05].CsA组和FK506组大鼠血钙浓度分别为(2.00±0.04)和(2.05_4-0.04)mmol/L,均低于FK506加Dil组和对照组(P＜0.05).CsA组和FK506组均可观察到肾小管细胞轻微肿胀及空泡变性、线粒体肿胀及空泡化等病理改变.与FK506组和CsA组相比,FK506加Dil组上述各项指标的变化明显减轻或接近正常.结论 钙离子代谢紊乱可能介导了FK506引起的肾毒性,Dil可用于预防FK506的肾毒性.
目的 觀察他剋莫司(FK506)腎毒性模型中鈣離子代謝的變化情況,探討鈣離子通道阻滯劑地爾硫草(Dil)對FK506腎毒性的預防作用.方法 按公式將腎移植術後FK506、環孢素(CsA)和Dil的首劑治療劑量換算成大鼠的治療劑量.雄性SD大鼠24隻隨機分成對照組、CsA組(25 mg·kg-1·d-1)、FK506組(0.8 mg·kg-1·d-1)和FK506加Dil組(0.8 mg·kg-1·d-1及8 mg·kg-1·d-1),每組6隻,用藥4週後建立各組大鼠腎毒性模型.觀察各組大鼠SCr、血電解質、腎組織的病理改變(HE染色)、電子顯微鏡F腎髒細胞內超微結構的改變.結果 CsA組和FK506組大鼠SCr值分彆為(36.00±2.61)和(34.17±4.54)μmol/L,均高于FK506加Dil組和對照組[(28.50±2.07)和(29.17±3.43)μmol/L,P＜0.05].CsA組和FK506組大鼠血鈣濃度分彆為(2.00±0.04)和(2.05_4-0.04)mmol/L,均低于FK506加Dil組和對照組(P＜0.05).CsA組和FK506組均可觀察到腎小管細胞輕微腫脹及空泡變性、線粒體腫脹及空泡化等病理改變.與FK506組和CsA組相比,FK506加Dil組上述各項指標的變化明顯減輕或接近正常.結論 鈣離子代謝紊亂可能介導瞭FK506引起的腎毒性,Dil可用于預防FK506的腎毒性.
목적 관찰타극막사(FK506)신독성모형중개리자대사적변화정황,탐토개리자통도조체제지이류초(Dil)대FK506신독성적예방작용.방법 안공식장신이식술후FK506、배포소(CsA)화Dil적수제치료제량환산성대서적치료제량.웅성SD대서24지수궤분성대조조、CsA조(25 mg·kg-1·d-1)、FK506조(0.8 mg·kg-1·d-1)화FK506가Dil조(0.8 mg·kg-1·d-1급8 mg·kg-1·d-1),매조6지,용약4주후건립각조대서신독성모형.관찰각조대서SCr、혈전해질、신조직적병리개변(HE염색)、전자현미경F신장세포내초미결구적개변.결과 CsA조화FK506조대서SCr치분별위(36.00±2.61)화(34.17±4.54)μmol/L,균고우FK506가Dil조화대조조[(28.50±2.07)화(29.17±3.43)μmol/L,P＜0.05].CsA조화FK506조대서혈개농도분별위(2.00±0.04)화(2.05_4-0.04)mmol/L,균저우FK506가Dil조화대조조(P＜0.05).CsA조화FK506조균가관찰도신소관세포경미종창급공포변성、선립체종창급공포화등병리개변.여FK506조화CsA조상비,FK506가Dil조상술각항지표적변화명현감경혹접근정상.결론 개리자대사문란가능개도료FK506인기적신독성,Dil가용우예방FK506적신독성.
Objective To study the calcium metabolism in tacrolimus(FK506)induced rats nephrotoxicity and the preventive effect of calcium channel blocker.Methods Twenty-four Spragueinduced or FK506-induced nephropathy model.Blood creatinine,blood electrolytes,renal tissue histopathology(HE stain)and the change of ultrastructural organization in renal cells by transmission electron microscope were observed.Results The blood creatinine levels of both CsA and FK506 groups [(36.00±2.61)and(34.17±4.54)μmol/L] were significantly higher than those of the FK506+Dilgroup and control group(all P＜0.05).The blood calcium levels of both CsA and FK506 groups (2.00±0.04 and 2.05±0.04 mmol/L) were significantly lower than those of the FK506+Dil group and control group(all P＜0.05).The blood creatinine and calcium levels of FK506+Dil group were not significantly different with those of control group(P＞O.05).Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells and intra-cellular mitochondria swelling and vacuolization in the CsA and FK506 groups.However,the pathological changes of the FK506+Dil group were remarkably milder in comparison with the CsA and FK506 groups.Concluum channel blocker,Dil,could prevent the FK506-induced nephrotoxicity.
