【摘要】：目的：研究重組肽HVGGSSV特異性靶向結(jié)合放射損傷腫瘤的能力，探討HVGGSSV在體內(nèi)的分布情況，，為腫瘤分子靶向治療提供一個(gè)新思路。 方法：用游離熒光染料Cy7-NHSester標(biāo)記多肽HVGGSSV，合成Cy7-HVGGSSV復(fù)合物。以雙后肢皮下接種人鼻咽癌細(xì)胞移植瘤的裸鼠作為實(shí)驗(yàn)?zāi)Ｐ?研究熒光多肽(Cy7-HVGGSSV)與放射損傷的腫瘤組織特異結(jié)合的靶向性。實(shí)驗(yàn)小鼠右后肢腫瘤給于6MV-X線3Gy放射處理，左后肢處腫瘤不接受放射線照射，隨機(jī)分為對(duì)照和實(shí)驗(yàn)組，每組5只裸鼠，放射后4小時(shí)從尾靜脈分別注射100ul游離Cy7-NHSester溶液和Cy7-HVGGSSV溶液。應(yīng)用小動(dòng)物活體成像系統(tǒng)檢測(cè)實(shí)驗(yàn)小鼠在注射藥物后不同時(shí)間點(diǎn)（1h，2h，15h，24h，48h）體內(nèi)熒光分布,并比較雙后肢腫瘤處的熒光量。48h后處死實(shí)驗(yàn)組小鼠，取出心、肺、肝、腎、腫瘤，觀察各臟器及腫瘤的熒光量分布。通過(guò)小動(dòng)物活體成像系統(tǒng)的軟件處理平臺(tái)在熒光分布圖上勾畫(huà)感興趣的區(qū)域(ROI)并測(cè)量其熒光量子，通過(guò)比較感興趣區(qū)域的總熒光量子判斷目標(biāo)區(qū)域的熒光分布強(qiáng)弱。 結(jié)果:1.在15h、24h觀察點(diǎn)，實(shí)驗(yàn)組（Cy7-HVGGSSV組）小鼠右后肢腫瘤較左后肢腫瘤熒光分布分別高4.04×107±2.66×107phontos/s/cm2、5.63×107±2.42×107phontos/s/cm2，p＜0.05。2.在1h、2h、15h、24h、48h等觀察點(diǎn)，實(shí)驗(yàn)組(Cy7-HVGGSSV組)較對(duì)照組(Cy7組)小鼠右后肢腫瘤區(qū)域的熒光量子高1.81×108±1.58×107phontos/s/cm2、1.28×108±3.49×107phontos/s/cm2、5.28×108±2.93×107phontos/s/cm2、6.0×108±2.69×107phontos/s/cm2、1.38×108±1.33×107phontos/s/cm2,p＜0.05。3.對(duì)照組小鼠的熒光分布無(wú)特異性，雙后肢腫瘤熒光量子無(wú)明顯差別。4.在注射后48小時(shí)，實(shí)驗(yàn)組小鼠體內(nèi)臟器的熒光分布顯示小鼠肝臟、腎臟具有較高的熒光量分布，而心臟、肺臟及腫瘤區(qū)域熒光分布較低。 結(jié)論：1.HVGGSSV可以特異性結(jié)合放射損傷的腫瘤組織，可以考慮作為放射引導(dǎo)藥物靶向運(yùn)輸?shù)妮d體；2.HVGGSSV可能通過(guò)肝臟及腎臟代謝。
[Abstract]:Objective: to study the ability of specific targeting of recombinant peptide HVGGSSV combined with radiation damage tumor, and to investigate the distribution of HVGGSSV in vivo, and to provide a new idea for tumor molecular targeted therapy. Methods: the free fluorescent dye Cy7-NHSester labeled polypeptide HVGGSSV, was used to synthesize Cy7-HVGGSSV complex. The specific binding of fluorescent polypeptide (Cy7-HVGGSSV) to radiation injured tumor was studied in nude mice inoculated subcutaneously with human nasopharyngeal carcinoma (NPC) cells in both hind limbs. The tumor of the right hind limb of the experimental mice was treated with 6MV-X line 3Gy radiation. The tumor of the left hind limb was not irradiated by radiation. The mice were randomly divided into control group and experimental group. Five nude mice in each group were injected 100ul free Cy7-NHSester solution and Cy7-HVGGSSV solution from caudal vein 4 hours after irradiation. The fluorescence distribution of experimental mice at different time points (1 h ~ 2 h ~ 15 h ~ 24 h ~ 48 h after injection) was detected by small animal imaging system in vivo. The mice in the experimental group were killed after the tumor of both hind limbs. The heart, lung, liver, kidney and tumor were taken out. The fluorescence distribution of various organs and tumors was observed. Using the software processing platform of small animal living imaging system, the (ROI) of the region of interest is drawn on the fluorescence distribution map and the fluorescence quantum of the region of interest is measured, and the intensity of the fluorescence distribution of the target region is judged by comparing the total fluorescence quantum of the region of interest. The result is 1: 1. The fluorescence distribution of tumor in the right hind limb of the experimental group (Cy7-HVGGSSV group) was 4.04 脳 107 鹵2.66 脳 10 ~ 7phontosr / s / cm _ 2 5.63 脳 10 ~ 7 鹵2.42 脳 10 ~ 7phontosr / s 路cm ~ (-2) P < 0.05.2, respectively, at the observation point of 15 h or 24 h. The fluorescence quantum in the tumor region of the right hind limb of the experimental group (Cy7-HVGGSSV group) was 1.81 脳 10 8 鹵1.58 脳 10 7phontosr / s / cm 2: 1.28 脳 10 8 鹵3.49 脳 10 7 phontosr / s / cm = 1.28 脳 10 8 鹵3.49 脳 10 7 phonons / s / cm = 1.28 脳 10 7 / s / cm = 2.93 脳 10 7 phonos / s / cm = 2. 0 脳 10 8 鹵2. 69 脳 10 7 phonons / s / cm 路cm ~ (-2) P < 0. 05. 3 脳 10 ~ 8 鹵1. 33 脳 10 ~ 7 / P / cm ~ (2) P < 0. 05.33 脳 10 ~ 7 / s / cm ~ (-1) P < 0.05.3 脳 10 ~ (7) / s / cm ~ (-1). The fluorescence distribution of mice in the control group was not specific, and the fluorescence quantum of tumor in both hind limbs was not significantly different. 4. At 48 hours after injection, the fluorescence distribution of the viscera in the experimental group showed that the liver and kidney of the experimental group had a higher fluorescence distribution, but the fluorescence distribution in the heart, lung and tumor areas was lower than that in the control group. Conclusion: 1. HVGGSSV can specifically bind to tumor tissue injured by radiation, and it can be considered as a carrier of radiation-guided drug targeting transport. 2. HVGGSSV may be metabolized through liver and kidney.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R730.55

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