中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2013年
12期
914-919
,共6页
潘晶晶%宣小燕%张爱华%丁桂霞
潘晶晶%宣小燕%張愛華%丁桂霞
반정정%선소연%장애화%정계하
顺铂%线粒体%急性肾损伤%肾损伤分子1%线粒体功能障碍
順鉑%線粒體%急性腎損傷%腎損傷分子1%線粒體功能障礙
순박%선립체%급성신손상%신손상분자1%선립체공능장애
Cisplatin%Mitochondria%Acute kidney injury%Kidney injury molecule-1%Mitochondrial dysfunction
目的 通过观察顺铂在不同剂量下诱导小鼠急性肾损伤的特点,进一步了解线粒体功能障碍参与急性肾损伤的机制.方法 雄性C57BL/6J小鼠18只,随机分为正常对照组(n=6)及顺铂处理组(n=12),其中顺铂处理组按顺铂给予剂量不同又分为10 mg/kg组(n=6)和20 mg/kg组(n=6).采用顺铂单次腹腔注射建立急性肾损伤模型,72 h后处死小鼠.测定肾功能相关生化指标、肾组织病理改变、肾损伤标志物的变化以及肾脏线粒体功能及结构变化指标.结果 (1)顺铂注射72 h后,顺铂处理组与对照组相比出现明显急性肾损伤表现,其中20 mg/kg组肾损伤程度更为严重,表现为随着顺铂剂量加大,肾生化指标血肌酐、尿蛋白等水平逐渐升高.(2)顺铂处理组肾小管结构破坏,蛋白管型形成,同时肾损伤标志物肾损伤分子1(KIM-1)mRNA升高(P＜0.05).(3)顺铂处理组肾小管线粒体结构破坏明显,同时线粒体DNA拷贝数下降(P＜0.05),线粒体相关蛋白过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1α)及ATP合酶表达降低(P＜0.01),细胞色素C从线粒体向胞质释放;且不同浓度顺铂组间各项指标差异亦有统计学意义(P＜0.05).结论 顺铂能够呈剂量依赖性的诱导急性肾损伤发生,线粒体功能障碍参与了肾损伤发生,并与肾损伤的病理改变密切相关.
目的 通過觀察順鉑在不同劑量下誘導小鼠急性腎損傷的特點,進一步瞭解線粒體功能障礙參與急性腎損傷的機製.方法 雄性C57BL/6J小鼠18隻,隨機分為正常對照組(n=6)及順鉑處理組(n=12),其中順鉑處理組按順鉑給予劑量不同又分為10 mg/kg組(n=6)和20 mg/kg組(n=6).採用順鉑單次腹腔註射建立急性腎損傷模型,72 h後處死小鼠.測定腎功能相關生化指標、腎組織病理改變、腎損傷標誌物的變化以及腎髒線粒體功能及結構變化指標.結果 (1)順鉑註射72 h後,順鉑處理組與對照組相比齣現明顯急性腎損傷錶現,其中20 mg/kg組腎損傷程度更為嚴重,錶現為隨著順鉑劑量加大,腎生化指標血肌酐、尿蛋白等水平逐漸升高.(2)順鉑處理組腎小管結構破壞,蛋白管型形成,同時腎損傷標誌物腎損傷分子1(KIM-1)mRNA升高(P＜0.05).(3)順鉑處理組腎小管線粒體結構破壞明顯,同時線粒體DNA拷貝數下降(P＜0.05),線粒體相關蛋白過氧化物酶體增殖活化受體γ輔助活化因子1α(PGC-1α)及ATP閤酶錶達降低(P＜0.01),細胞色素C從線粒體嚮胞質釋放;且不同濃度順鉑組間各項指標差異亦有統計學意義(P＜0.05).結論 順鉑能夠呈劑量依賴性的誘導急性腎損傷髮生,線粒體功能障礙參與瞭腎損傷髮生,併與腎損傷的病理改變密切相關.
목적 통과관찰순박재불동제량하유도소서급성신손상적특점,진일보료해선립체공능장애삼여급성신손상적궤제.방법 웅성C57BL/6J소서18지,수궤분위정상대조조(n=6)급순박처리조(n=12),기중순박처리조안순박급여제량불동우분위10 mg/kg조(n=6)화20 mg/kg조(n=6).채용순박단차복강주사건립급성신손상모형,72 h후처사소서.측정신공능상관생화지표、신조직병리개변、신손상표지물적변화이급신장선립체공능급결구변화지표.결과 (1)순박주사72 h후,순박처리조여대조조상비출현명현급성신손상표현,기중20 mg/kg조신손상정도경위엄중,표현위수착순박제량가대,신생화지표혈기항、뇨단백등수평축점승고.(2)순박처리조신소관결구파배,단백관형형성,동시신손상표지물신손상분자1(KIM-1)mRNA승고(P＜0.05).(3)순박처리조신소관선립체결구파배명현,동시선립체DNA고패수하강(P＜0.05),선립체상관단백과양화물매체증식활화수체γ보조활화인자1α(PGC-1α)급ATP합매표체강저(P＜0.01),세포색소C종선립체향포질석방;차불동농도순박조간각항지표차이역유통계학의의(P＜0.05).결론 순박능구정제량의뢰성적유도급성신손상발생,선립체공능장애삼여료신손상발생,병여신손상적병리개변밀절상관.
Objective To assess the characteristics of different doses of cisplatin-induced acute kidney injury,further to understand mitochondrial dysfunction and its role in acute kidney injury (AKI).Methods Male C57BL/6J mice were first randomly divided into two groups:control group (n =6) and AKI group (n =12).Then,AKI group was subsequently divided into other two groups according to different dose of cisplatin (10 mg/kg or 20 mg/kg).AKI group received intraperitoneal injection of cisplatin.All mice were sacrificed after 72 h of injection.Renal biochemical function,renal pathological changes,renal injury markers,kidney mitochondrial function and structural changes were observed.Results (1) After 72 hours of injection,the AKI group performed significant kidney injury changes compared to control group,thereinto 20 mg/kg group was more serious than 10 mg/kg group.With the cisplatin dose increasing,renal function markers such as serum creatinine,urine protein gradually increased.(2)Kidney biopsy showed tubular structural damage,the formation of protein casts,kidney injury molecule-1 (KIM-1) gradually increased(P ＜ 0.05).(3)Electron microscopy found tubular mitochondrial structural damage,mtDNA copy number decreased,the level of peroxisome proliferatoractivated receptor-gamma coactivator-1alpha (PGC-1α),ATP synthase β decreased(P ＜ 0.05),and Western blotting manifested cytochrome C was released from mitochondria to the cytoplasm.These data all exhibited significant difference between different groups(P ＜ 0.05).Conclusions Cisplatin induces acute kidney injury in dose-dependent manner.Mitochondrial dysfunction participates in kidney injury,and is also related to the kidney pathological damage.
