中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2009年
10期
704-708
,共5页
陈业辉%梁颜笑%陈林强%路艳蒙%梁健健%张静%邱江%谢克基%胡建波%钟惟德%王斌%陈立中%郑克立
陳業輝%樑顏笑%陳林彊%路豔矇%樑健健%張靜%邱江%謝剋基%鬍建波%鐘惟德%王斌%陳立中%鄭剋立
진업휘%량안소%진림강%로염몽%량건건%장정%구강%사극기%호건파%종유덕%왕빈%진립중%정극립
地尔硫革%病理学%他克莫司%肾毒性%超微结构
地爾硫革%病理學%他剋莫司%腎毒性%超微結構
지이류혁%병이학%타극막사%신독성%초미결구
Diltiazem%Pathology%Tacrolimus%Nephrotoxicity%Ultrastructural organization
目的 探讨肾移植术后首剂治疗剂量他克莫司(FK506)对大鼠肾脏组织和肾脏细胞超微结构的影响,以及地尔硫革(Dil)对FK506肾毒性的防治作用.方法 按公式将肾移植术后FK506、环孢素A(CsA)和Dil的首剂治疗剂最换算成大鼠的治疗剂量.SD大鼠2,4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+Dil组(0.8 mg·kg-1·d1及8 mg·kg-1·d-1),用药4周后建立起各组大鼠肾毒性模型.观察各组大鼠的肾功能指标、肾组织的病理改变(HE染色、PAS染色和MASSON染色)、电子显微镜下肾脏细胞内超微结构的改变.结果 CsA组与FKS06组出现明显的血肌酐上升(36.0±2.6)、(34.2±4.5)μmol/L,对照组为(29.2±3.4)μmol/L;肌酐清除率下降(0.63±0.45)、(0.58±0.39)ml·min-1·100 g-1,而对照组、FK506+Dil组为(1.55±0.91)、(1.02±0.62)ml·min-1·100 g-1.两组均可观察到明显的肾小管细胞浊肿及空泡变性,并且出现不同程度的肾内小动脉玻璃样变、肾小管间质纤维化、肾小球足细胞融合、肾小管上皮细胞线粒体肿胀空泡化等病变.FK506+Dil组上述各项指标的变化有所减轻或接近正常.结论 肾移植术后首剂治疗剂量FK506与CsA一样,均可引起大鼠肾脏组织和肾脏细胞超微结构出现病理改变.地尔硫革可以减轻FK506对肾脏组织和细胞的病理损害.
目的 探討腎移植術後首劑治療劑量他剋莫司(FK506)對大鼠腎髒組織和腎髒細胞超微結構的影響,以及地爾硫革(Dil)對FK506腎毒性的防治作用.方法 按公式將腎移植術後FK506、環孢素A(CsA)和Dil的首劑治療劑最換算成大鼠的治療劑量.SD大鼠2,4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+Dil組(0.8 mg·kg-1·d1及8 mg·kg-1·d-1),用藥4週後建立起各組大鼠腎毒性模型.觀察各組大鼠的腎功能指標、腎組織的病理改變(HE染色、PAS染色和MASSON染色)、電子顯微鏡下腎髒細胞內超微結構的改變.結果 CsA組與FKS06組齣現明顯的血肌酐上升(36.0±2.6)、(34.2±4.5)μmol/L,對照組為(29.2±3.4)μmol/L;肌酐清除率下降(0.63±0.45)、(0.58±0.39)ml·min-1·100 g-1,而對照組、FK506+Dil組為(1.55±0.91)、(1.02±0.62)ml·min-1·100 g-1.兩組均可觀察到明顯的腎小管細胞濁腫及空泡變性,併且齣現不同程度的腎內小動脈玻璃樣變、腎小管間質纖維化、腎小毬足細胞融閤、腎小管上皮細胞線粒體腫脹空泡化等病變.FK506+Dil組上述各項指標的變化有所減輕或接近正常.結論 腎移植術後首劑治療劑量FK506與CsA一樣,均可引起大鼠腎髒組織和腎髒細胞超微結構齣現病理改變.地爾硫革可以減輕FK506對腎髒組織和細胞的病理損害.
목적 탐토신이식술후수제치료제량타극막사(FK506)대대서신장조직화신장세포초미결구적영향,이급지이류혁(Dil)대FK506신독성적방치작용.방법 안공식장신이식술후FK506、배포소A(CsA)화Dil적수제치료제최환산성대서적치료제량.SD대서2,4지수궤분성대조조、CsA조(25 mg·kg-1·d-1)、FK506조(0.8 mg·kg-1·d-1)화FK506+Dil조(0.8 mg·kg-1·d1급8 mg·kg-1·d-1),용약4주후건립기각조대서신독성모형.관찰각조대서적신공능지표、신조직적병리개변(HE염색、PAS염색화MASSON염색)、전자현미경하신장세포내초미결구적개변.결과 CsA조여FKS06조출현명현적혈기항상승(36.0±2.6)、(34.2±4.5)μmol/L,대조조위(29.2±3.4)μmol/L;기항청제솔하강(0.63±0.45)、(0.58±0.39)ml·min-1·100 g-1,이대조조、FK506+Dil조위(1.55±0.91)、(1.02±0.62)ml·min-1·100 g-1.량조균가관찰도명현적신소관세포탁종급공포변성,병차출현불동정도적신내소동맥파리양변、신소관간질섬유화、신소구족세포융합、신소관상피세포선립체종창공포화등병변.FK506+Dil조상술각항지표적변화유소감경혹접근정상.결론 신이식술후수제치료제량FK506여CsA일양,균가인기대서신장조직화신장세포초미결구출현병리개변.지이류혁가이감경FK506대신장조직화세포적병리손해.
Objective To study the nephrotoxicity tacrolimus (FK506) at the therapeutic dose the preventive effect of diltiazem (Dil), a calcium antagonist against the FK506-induced pathological changes. Methods 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: cyclosporine A (CsA) group, undergoing treatment of CsA at the therapeutic dose after kidney transplantation (25 mg·kg-1·d-1) for 4 weeks, FK506 group treated with FK506 (0.8 mg·kg1·d-1), FK506 + Dil group treated with FK506 (0.8 mg·kg-1·d-1) and Dil at the dose of 8 mg·kg-1·d-1, and control group. Four weeks later body weight was measured and 24 h urine sample was collected. Then the rats were killed. Their kidneys underwent light and transmission electron microscopy. Results The body weight ad weight gain, and the weights of both kidney of the CsA group were all significantly lower than those of the other 3 groups (all P<0.05), and there were not significant differences in there parameters among the other 3 groups. The serum creatinine levels of the FK506 and CsA groups were (36.0±2.6) and (34.2±4.5) μmol/L respectively, both significantly higher than those of the FK506 + Dil and control groups [(28.5±2.1) and (29.2±3.428)μmol/L respectively, all P<0.05], however, there was no significant difference between the FK506 + Dil and control groups. The creatinine clearance rate of the FK506 and CsA groups were (0.63±0.45) and (0.58±0.39)ml·min-1·100 g-1 respectively, significantly lower than those of the FK506 + Dil and control groups [(1.55±0.91) and (1.02±0.62) ml·min-1·100 g-1 respectively, all P<0.05]. Pathological examination showed epithelial cell cloudy swelling and vaeuolization and interstitial fibrosis in the renal tubules, mitochondria swelling and vacuolization in renal tubular epithelial cells, renal arteriole hyalinization, and foot cell conjugation glomerulus, mitochondria swelling and vacuolization in the FK506 and CsA groups, and such changes were relatively mild in the FK506 + Dil group. Conclusion FK506 at renal transplantation therapeutic dose, as well as CsA, induces pathological changes in renal tissues and ultrastructural organization. Dil is able to prevent FK506-induced these pathological changes.
