运动联合肿瘤靶向给药系统对小鼠种植性肝癌治疗效果的研究

发布时间：2018-03-25 08:05

本文选题：运动　切入点：肿瘤靶向给药系统　出处：《扬州大学》2012年硕士论文

【摘要】：实验目的：建立荷Hepal-6肿瘤C57BL/6小鼠模型,观察运动联合肿瘤靶向给药系统mPEG-PLGA-PLL-cRGD对小鼠种植性肝癌治疗效果的,探讨运动影响肿瘤生长的可能机制。实验方法：实验一：制备肿瘤靶向给药系统载体材料mPEG-PLGA-PLL-cRGD,并对载体材料进行表征。用载体材料制备载药纳米粒,并观察其包封率和载药量。实验二：选取雄性6～8周龄C57BL/6小鼠建立荷Hepal-6中瘤模型,选择建模成功的小鼠78只随机分为对照组(FREE)、运动组(SP)、米托蒽醌组(DHAQ)、载DHAQ纳米粒组(NPS)、运动联合米托葸醌组(SP+DHAQ)、运动联合载DHAQ纳米粒组(SP+NPS)。药物经腹腔注入小鼠体内,并给予运动组、运动联合米托蒽醌组(SP+DHAQ)、运动联合载DHAQ纳米粒组(SP+NPS)小鼠一定强度、持续14天的运动。实验期间每两天测量小鼠体重和肿瘤体积。运动结束后测定FREE组、SP组、DHAQ组、NPS组、SP+DHAQ组、SP+NPS组小鼠血清NO含量和肿瘤H2S含量。实验结果： 1.肿瘤靶向给药系统载体材料mPEG-PLGA-PLL-cRGD成功合成。 2.14天治疗后,SP组抑瘤率为15.7%,DHAQ组抑瘤率为19.13%,NPS组抑瘤率为28.08%,SP+DHAQ组抑瘤率为14.57%,SP+NPS组抑瘤率为36.14%。 3.14天运动后,SP组、SP+DHAQ组、SP+NPS组小鼠血清NO含量均明显高于FREE组,DHAQ组和NPS组小鼠血清NO含量较FREE组无明显差异。 4.14天运动后,SP组、SP+DHAQ组、SP+NPS组小鼠肿瘤H2S含量均明显高于FREE组,DHAQ组和NPS组小鼠肿瘤H2S含量较FREE组无明显差异。结论： 1.运动联合肿瘤靶向给药系统能有效抑制小鼠种植性肝癌的生长。运动对靶向给药系统抑制肿瘤生长有协同作用。适宜的运动能增强活性肽修饰的载体材料构成的肿瘤靶向给药系统对小鼠种植性肝癌的治疗效果。 2.适宜的运动后,SP组、SP+DHAQ组、SP+NPS组小鼠体内NO和H2S含量均明显高于FREE组。但SP组和SP+DHAQ组小鼠肿瘤体积的增长并未被明显抑制。提示运动增强肿瘤靶向给药系统对小鼠肿瘤治疗效果的机制可能是运动增加体内NO和H2S的表达,使得载体材料将肿瘤药物更多的靶向肿瘤,导致肿瘤生长的抑制。
[Abstract]:Objective: to establish Hepal-6 tumor C57BL/6 mice model, observe the therapeutic effect of exercise combined with tumor targeting drug delivery system (mPEG-PLGA-PLL-cRGD) on implanted liver cancer in mice, and explore the possible mechanism of exercise affecting tumor growth. Methods: experiment 1: preparation and characterization of mPEG-PLGA-PLL-cRGD.The carrier materials were used to prepare drug-loaded nanoparticles. The encapsulation efficiency and drug loading capacity were observed. Experiment 2: the tumor model of Hepal-6 was established by selecting the male C57BL/6 mice at the age of 68 weeks. Seventy-eight mice with successful modeling were randomly divided into three groups: control group, exercise group, mitoxantrone group, mitoxantrone group, DHAQ nanoparticles group, exercise combined with mitoxantrone group, and exercise combined with DHAQ nanoparticles group. The drug was injected intraperitoneally into mice. Exercise combined with mitoxantrone group and exercise combined with DHAQ nanoparticles group were given to mice with certain intensity. The body weight and tumor volume of mice were measured every two days during the experiment. After exercise, the serum no content and tumor H2S content in FREE group (SP group) and SP DHAQ group (SP DHAQ group) were measured. Experimental results:. 1. MPEG-PLGA-PLL-cRGD, the carrier material of tumor targeting drug delivery system, was successfully synthesized. 2.14 days after treatment, the tumor inhibition rate of SP group was 15.7and 19.13% respectively. The inhibition rate of SP DHAQ group was 28.08%. The inhibition rate of SP DHAQ group was 14.57%. The inhibition rate of SP NPS group was 36.14%. 3. After 14 days exercise, the serum no levels in SP DHAQ group were significantly higher than those in FREE group and NPS group compared with FREE group. 4. After 14 days exercise, the tumor H2S content in SP DHAQ group was significantly higher than that in FREE group and NPS group. There was no significant difference in H2S content between FREE group and FREE group. Conclusion:. 1. Exercise combined with tumor targeting drug delivery system can effectively inhibit the growth of implanted liver cancer in mice. Exercise has synergistic effect on the inhibition of tumor growth by targeted drug delivery system. Proper exercise can enhance the composition of carrier modified with active peptide. Effect of tumor targeting drug delivery system on implanted liver cancer in mice. 2. The contents of no and H2S in SP DHAQ group were significantly higher than those in FREE group, but the tumor volume in SP group and SP DHAQ group were not significantly inhibited, suggesting that exercise could enhance the tumor targeting drug delivery system. The mechanism of tumor therapy in mice may be that exercise can increase the expression of no and H2S in mice. So that the carrier materials will be more targeted tumor drugs, leading to tumor growth inhibition.
【学位授予单位】：扬州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R455;R735.7;R730.53

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