中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2014年
10期
746-750
,共5页
张永明%张兴华%唐万燕%马洁
張永明%張興華%唐萬燕%馬潔
장영명%장흥화%당만연%마길
聚乙二醇类%柔红霉素%脂质体%白血病%荷瘤鼠%治疗结果%药物毒性
聚乙二醇類%柔紅黴素%脂質體%白血病%荷瘤鼠%治療結果%藥物毒性
취을이순류%유홍매소%지질체%백혈병%하류서%치료결과%약물독성
Polyethylene glycols%Daunorubicin%Liposomes%Leukemia%Mice%Treatment outcome%Drug toxicity
目的 探讨聚乙二醇(PEG)修饰的柔红霉素(DNR)脂质体(PL-DNR)治疗白血病的疗效及其毒副作用.方法 采用薄层水化法和主动载药法制备PL-DNR,测定理化指标,进行体外细胞增殖抑制实验,分析PL-DNR对白血病细胞的杀伤作用.利用L1210荷瘤鼠白血病模型评价PL-DNR的体内抑瘤效果.采用原位末端转移酶标记法分析药物对小鼠的心肌毒性.结果 PL-DNR粒径大小为(110±10)nm,包封率为94.21％.体外增殖抑制实验显示,PL-DNR的抑瘤能力随实验时间延长逐渐增强.体内药效学实验显示,PL-DNR抑瘤效果明显,PL-DNR组和DNR组的肿瘤体积分别为(433.71±234.77) mm3和(1 293.77±381.26) mm3,差异有统计学意义(P＜0.05).PL-DNR组和DNR组的瘤重分别为(0.66 ±0.29)g和(1.25 ±0.43)g,差异有统计学意义(P＜0.05).心肌毒性实验显示,PL-DNR组和DNR组小鼠的心肌组织中位凋亡细胞阳性指数分别为13.83％和42.67％(P＜0.05).结论 与柔红霉素相比,PEG修饰的柔红霉素脂质体可提高原药对白血病的治疗效果,同时降低对心肌的毒副作用.
目的 探討聚乙二醇(PEG)脩飾的柔紅黴素(DNR)脂質體(PL-DNR)治療白血病的療效及其毒副作用.方法 採用薄層水化法和主動載藥法製備PL-DNR,測定理化指標,進行體外細胞增殖抑製實驗,分析PL-DNR對白血病細胞的殺傷作用.利用L1210荷瘤鼠白血病模型評價PL-DNR的體內抑瘤效果.採用原位末耑轉移酶標記法分析藥物對小鼠的心肌毒性.結果 PL-DNR粒徑大小為(110±10)nm,包封率為94.21％.體外增殖抑製實驗顯示,PL-DNR的抑瘤能力隨實驗時間延長逐漸增彊.體內藥效學實驗顯示,PL-DNR抑瘤效果明顯,PL-DNR組和DNR組的腫瘤體積分彆為(433.71±234.77) mm3和(1 293.77±381.26) mm3,差異有統計學意義(P＜0.05).PL-DNR組和DNR組的瘤重分彆為(0.66 ±0.29)g和(1.25 ±0.43)g,差異有統計學意義(P＜0.05).心肌毒性實驗顯示,PL-DNR組和DNR組小鼠的心肌組織中位凋亡細胞暘性指數分彆為13.83％和42.67％(P＜0.05).結論 與柔紅黴素相比,PEG脩飾的柔紅黴素脂質體可提高原藥對白血病的治療效果,同時降低對心肌的毒副作用.
목적 탐토취을이순(PEG)수식적유홍매소(DNR)지질체(PL-DNR)치료백혈병적료효급기독부작용.방법 채용박층수화법화주동재약법제비PL-DNR,측정이화지표,진행체외세포증식억제실험,분석PL-DNR대백혈병세포적살상작용.이용L1210하류서백혈병모형평개PL-DNR적체내억류효과.채용원위말단전이매표기법분석약물대소서적심기독성.결과 PL-DNR립경대소위(110±10)nm,포봉솔위94.21％.체외증식억제실험현시,PL-DNR적억류능력수실험시간연장축점증강.체내약효학실험현시,PL-DNR억류효과명현,PL-DNR조화DNR조적종류체적분별위(433.71±234.77) mm3화(1 293.77±381.26) mm3,차이유통계학의의(P＜0.05).PL-DNR조화DNR조적류중분별위(0.66 ±0.29)g화(1.25 ±0.43)g,차이유통계학의의(P＜0.05).심기독성실험현시,PL-DNR조화DNR조소서적심기조직중위조망세포양성지수분별위13.83％화42.67％(P＜0.05).결론 여유홍매소상비,PEG수식적유홍매소지질체가제고원약대백혈병적치료효과,동시강저대심기적독부작용.
Objective To explore the antitumor effect and toxicity of pegylated liposomal daunorubicin (PL-DNR) on leukemia.Methods PL-DNR was prepared by dry lipid hydration and remote loading,and its physicochemical indexes were analyzed.The inhibiting effect of PL-DNR on leukemia cells was observed in terms of in vitro cytotoxicity experiment.The therapeutic effect in vivo was assessed by tumor inhibition in leukemia L1210-bearing mice.Apoptosis in cardiomyocytes was detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method (TUNEL staining).Results The average diameter of PL-DNR was (110 ± 10) nm and the encapsulation efficiency was 94.21％.The in vitro cytotoxicity experiment showed that the inhibiting ability of PL-DNR in the treatment groups was continuously enhanced as the experiment proceeded.The in vivo pharmacodynamic experiment also indicated obvious tumor-inhibiting effect of PL-DNR.At the end of the experiment,the tumor volume of the PL-DNR group was (433.71 ± 234.77) mm3,significantly smaller than that of (1 293.77 ± 381.26) mm3 in the DNR group (P ＜ 0.05).Moreover,the tumor weight of the PL-DNR group was (0.66 ± 0.29) g and that of the DNR group was (1.25 ± 0.43) g (P ＜ 0.05).The myocardial toxicity experiment showed that the median apoptosis index of cardiomyocytes in the PL-DNR group was 13.83％,significantly lower than that of 42.67％ in the DNR group (P ＜0.05),indicating a lower toxicity of PL-DNR to the myocardium.Conclusion Compared with the free DNR,PL-DNR can improve the therapeutic effect on leukemia and reduce the cardiotoxicity.
