中国药物警戒
中國藥物警戒
중국약물경계
CHINESE JOURNAL OF PHARMACOVIGILANCE
2014年
5期
257-260,263
,共5页
张友文%魏怀玲%鲍秀琦%张丹%孙华
張友文%魏懷玲%鮑秀琦%張丹%孫華
장우문%위부령%포수기%장단%손화
双环醇%顺铂%吉西他滨%肝肾损伤%非小细胞肺癌
雙環醇%順鉑%吉西他濱%肝腎損傷%非小細胞肺癌
쌍배순%순박%길서타빈%간신손상%비소세포폐암
bicyclol%cisplatin%gemcitabine%drug-induced liver and kidney injury%non-small cell lung cancer
目的:建立顺铂(CDDP)联合吉西他滨(GEM)引起小鼠肝肾损伤动物模型,研究双环醇对CDDP/GEM联用致荷瘤小鼠肝肾损伤及骨髓毒性的保护作用。方法参考临床用药方案,建立CDDP/GEM联用致小鼠肝肾损伤模型。在模型建立的基础上,考察双环醇的保护作用:C57/BL小鼠接种Lewis肺癌后第6天开始腹腔注射CDDP(5mg·kg-1×5)及GEM(50mg·kg-1×2),建立大剂量CDDP/GEM联用致小鼠肝肾损伤模型,同时灌胃给予双环醇(150、300mg·kg-1),以吉粒芬(100 g·kg-1)作为阳性对照药。于开始给药后第6天处理动物,取瘤称重,全自动生化分析仪检测血清肝功能及肾功能生化指标,五分类血液分析仪进行血象分析。结果小鼠腹腔注射CDDP(5mg·kg-1×5)及GEM (50mg·kg-1×2),在动物尚未出现大量死亡的情况下,能引起明显的肝肾损伤。双环醇150mg·kg-1能显著降低上述方案CDDP/GEM引起的血清CR的升高,同时显著升高全血中NEUT和NEUT%。双环醇300mg·kg-1亦有保护作用,但作用不显著。吉粒芬对CDDP/GEM联用引起的WBC、NEUT、NEUT%降低有显著升高作用。双环醇及吉粒芬与CDDP/GEM合用,对后者的抑瘤活性略有增加作用。结论双环醇在略增加CDDP/GEM抑瘤活性的基础上,150mg·kg-1剂量对后者引起的荷瘤小鼠肝肾损伤及骨髓毒性具有良好的保护作用,300mg·kg-1剂量组作用不及150mg·kg-1剂量组,但均能降低荷瘤小鼠死亡率,值得临床关注。
目的:建立順鉑(CDDP)聯閤吉西他濱(GEM)引起小鼠肝腎損傷動物模型,研究雙環醇對CDDP/GEM聯用緻荷瘤小鼠肝腎損傷及骨髓毒性的保護作用。方法參攷臨床用藥方案,建立CDDP/GEM聯用緻小鼠肝腎損傷模型。在模型建立的基礎上,攷察雙環醇的保護作用:C57/BL小鼠接種Lewis肺癌後第6天開始腹腔註射CDDP(5mg·kg-1×5)及GEM(50mg·kg-1×2),建立大劑量CDDP/GEM聯用緻小鼠肝腎損傷模型,同時灌胃給予雙環醇(150、300mg·kg-1),以吉粒芬(100 g·kg-1)作為暘性對照藥。于開始給藥後第6天處理動物,取瘤稱重,全自動生化分析儀檢測血清肝功能及腎功能生化指標,五分類血液分析儀進行血象分析。結果小鼠腹腔註射CDDP(5mg·kg-1×5)及GEM (50mg·kg-1×2),在動物尚未齣現大量死亡的情況下,能引起明顯的肝腎損傷。雙環醇150mg·kg-1能顯著降低上述方案CDDP/GEM引起的血清CR的升高,同時顯著升高全血中NEUT和NEUT%。雙環醇300mg·kg-1亦有保護作用,但作用不顯著。吉粒芬對CDDP/GEM聯用引起的WBC、NEUT、NEUT%降低有顯著升高作用。雙環醇及吉粒芬與CDDP/GEM閤用,對後者的抑瘤活性略有增加作用。結論雙環醇在略增加CDDP/GEM抑瘤活性的基礎上,150mg·kg-1劑量對後者引起的荷瘤小鼠肝腎損傷及骨髓毒性具有良好的保護作用,300mg·kg-1劑量組作用不及150mg·kg-1劑量組,但均能降低荷瘤小鼠死亡率,值得臨床關註。
목적:건립순박(CDDP)연합길서타빈(GEM)인기소서간신손상동물모형,연구쌍배순대CDDP/GEM련용치하류소서간신손상급골수독성적보호작용。방법삼고림상용약방안,건립CDDP/GEM련용치소서간신손상모형。재모형건립적기출상,고찰쌍배순적보호작용:C57/BL소서접충Lewis폐암후제6천개시복강주사CDDP(5mg·kg-1×5)급GEM(50mg·kg-1×2),건립대제량CDDP/GEM련용치소서간신손상모형,동시관위급여쌍배순(150、300mg·kg-1),이길립분(100 g·kg-1)작위양성대조약。우개시급약후제6천처리동물,취류칭중,전자동생화분석의검측혈청간공능급신공능생화지표,오분류혈액분석의진행혈상분석。결과소서복강주사CDDP(5mg·kg-1×5)급GEM (50mg·kg-1×2),재동물상미출현대량사망적정황하,능인기명현적간신손상。쌍배순150mg·kg-1능현저강저상술방안CDDP/GEM인기적혈청CR적승고,동시현저승고전혈중NEUT화NEUT%。쌍배순300mg·kg-1역유보호작용,단작용불현저。길립분대CDDP/GEM련용인기적WBC、NEUT、NEUT%강저유현저승고작용。쌍배순급길립분여CDDP/GEM합용,대후자적억류활성략유증가작용。결론쌍배순재략증가CDDP/GEM억류활성적기출상,150mg·kg-1제량대후자인기적하류소서간신손상급골수독성구유량호적보호작용,300mg·kg-1제량조작용불급150mg·kg-1제량조,단균능강저하류소서사망솔,치득림상관주。
Objective To determine the effect of bicyclol on cisplatin plus gemcitabine induced liver and kidney injury in tumor-bearing mice. Methods C57/BL mice implanted with Lewis lung tumors for 6 days were treated with cisplatin (5mg·kg-1×5) and gemcitabine(50mg·kg-1×2) to establish the liver damage model. Bicyclol(150, 300mg·kg-1) was pretreated 1h before the injection of cisplatin/gemcitabine while rhG-CSF was setted as the positive control. All animals were killed on the sixth day after cisplatin/gemcitabine treatment starting. We used automatic biochemistry analyzer and the automatic blood analyzer to detect kinds of blood indicators about liver, renal and bone marrow functions. Results The combination therapy of cisplatin and gemcitabine apparently induced the liver and kidney damage in C57/BL mice. Bicyclol(150mg·kg-1) significantly reduced CR levels and elevated the NEUT and NEUT% in the serum dam-aged by cisplatin/gemcitabine in tumor-bearing mice. Bicycle 300mg/kg also showed the protection effect, but there was no statistical significance. RhG-CSF, the positive control, could significantly increase the WBC, NEUT and NEUT%levels reduced by cisplatin/gemcitabine. Bicyclol and rhG-CSF also slightly increased the antitumor activity of cisplatin/gemcitabine in Lewis lung tumor. Conclusion Bicyclol, especially the 150mg/kg dose, showed the potent protective activity against cisplatin/gemcitabine-induced liver and renal damage. It could decrease the mortality rate by the high-dose chemotherapy and slightly increase the associated anti-tumor effect. This may provide a new approach for preventing the hepatotoxicity and nephrotoxicity induced by cisplatin/gemcitabine in the clinic.