運(yùn)動(dòng)聯(lián)合腫瘤靶向給藥系統(tǒng)對(duì)小鼠種植性肝癌治療效果的研究
本文選題:運(yùn)動(dòng) 切入點(diǎn):腫瘤靶向給藥系統(tǒng) 出處:《揚(yáng)州大學(xué)》2012年碩士論文
【摘要】:實(shí)驗(yàn)?zāi)康模航⒑蒆epal-6腫瘤C57BL/6小鼠模型,觀察運(yùn)動(dòng)聯(lián)合腫瘤靶向給藥系統(tǒng)mPEG-PLGA-PLL-cRGD對(duì)小鼠種植性肝癌治療效果的,探討運(yùn)動(dòng)影響腫瘤生長(zhǎng)的可能機(jī)制。 實(shí)驗(yàn)方法:實(shí)驗(yàn)一:制備腫瘤靶向給藥系統(tǒng)載體材料mPEG-PLGA-PLL-cRGD,并對(duì)載體材料進(jìn)行表征。用載體材料制備載藥納米粒,并觀察其包封率和載藥量。實(shí)驗(yàn)二:選取雄性6~8周齡C57BL/6小鼠建立荷Hepal-6中瘤模型,選擇建模成功的小鼠78只隨機(jī)分為對(duì)照組(FREE)、運(yùn)動(dòng)組(SP)、米托蒽醌組(DHAQ)、載DHAQ納米粒組(NPS)、運(yùn)動(dòng)聯(lián)合米托葸醌組(SP+DHAQ)、運(yùn)動(dòng)聯(lián)合載DHAQ納米粒組(SP+NPS)。藥物經(jīng)腹腔注入小鼠體內(nèi),并給予運(yùn)動(dòng)組、運(yùn)動(dòng)聯(lián)合米托蒽醌組(SP+DHAQ)、運(yùn)動(dòng)聯(lián)合載DHAQ納米粒組(SP+NPS)小鼠一定強(qiáng)度、持續(xù)14天的運(yùn)動(dòng)。實(shí)驗(yàn)期間每?jī)商鞙y(cè)量小鼠體重和腫瘤體積。運(yùn)動(dòng)結(jié)束后測(cè)定FREE組、SP組、DHAQ組、NPS組、SP+DHAQ組、SP+NPS組小鼠血清NO含量和腫瘤H2S含量。 實(shí)驗(yàn)結(jié)果: 1.腫瘤靶向給藥系統(tǒng)載體材料mPEG-PLGA-PLL-cRGD成功合成。 2.14天治療后,SP組抑瘤率為15.7%,DHAQ組抑瘤率為19.13%,NPS組抑瘤率為28.08%,SP+DHAQ組抑瘤率為14.57%,SP+NPS組抑瘤率為36.14%。 3.14天運(yùn)動(dòng)后,SP組、SP+DHAQ組、SP+NPS組小鼠血清NO含量均明顯高于FREE組,DHAQ組和NPS組小鼠血清NO含量較FREE組無(wú)明顯差異。 4.14天運(yùn)動(dòng)后,SP組、SP+DHAQ組、SP+NPS組小鼠腫瘤H2S含量均明顯高于FREE組,DHAQ組和NPS組小鼠腫瘤H2S含量較FREE組無(wú)明顯差異。 結(jié)論: 1.運(yùn)動(dòng)聯(lián)合腫瘤靶向給藥系統(tǒng)能有效抑制小鼠種植性肝癌的生長(zhǎng)。運(yùn)動(dòng)對(duì)靶向給藥系統(tǒng)抑制腫瘤生長(zhǎng)有協(xié)同作用。適宜的運(yùn)動(dòng)能增強(qiáng)活性肽修飾的載體材料構(gòu)成的腫瘤靶向給藥系統(tǒng)對(duì)小鼠種植性肝癌的治療效果。 2.適宜的運(yùn)動(dòng)后,SP組、SP+DHAQ組、SP+NPS組小鼠體內(nèi)NO和H2S含量均明顯高于FREE組。但SP組和SP+DHAQ組小鼠腫瘤體積的增長(zhǎng)并未被明顯抑制。提示運(yùn)動(dòng)增強(qiáng)腫瘤靶向給藥系統(tǒng)對(duì)小鼠腫瘤治療效果的機(jī)制可能是運(yùn)動(dòng)增加體內(nèi)NO和H2S的表達(dá),使得載體材料將腫瘤藥物更多的靶向腫瘤,導(dǎo)致腫瘤生長(zhǎng)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.
【學(xué)位授予單位】:揚(yáng)州大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R455;R735.7;R730.53
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