本文選題：光動(dòng)力 + 裸鼠QBC939膽管癌皮下移植瘤模型��； 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究背景和目的:肝臟膽管細(xì)胞癌(cholangiocarcinoma,CC)惡性程度高、侵襲性強(qiáng)、發(fā)病隱匿、是我國膽道系統(tǒng)常見的、死亡率較高的惡性腫瘤之一。根治性切除術(shù)是治愈膽管癌的唯一手段,然而臨床上可以進(jìn)行根治性切除的患者低于10%。光動(dòng)力(photodynamic therapy PDT)在國外是一種比較成熟的膽管癌治療手段,而在我國臨床上應(yīng)用金絲桃素作為光敏劑進(jìn)行膽管癌局部治療還相對(duì)較少。膽管癌惡性程度高,腫瘤血管生成、細(xì)胞增殖是病變進(jìn)展的重要生物學(xué)行為,直接決定其惡性程度。本課題以人QBC939膽管癌皮下荷瘤裸鼠模型為基礎(chǔ),利用金絲桃素作為光敏劑進(jìn)行光動(dòng)力治療,利用磁共振平掃T1WIT2WI、彌散加權(quán)成像(DWI)對(duì)光動(dòng)力治療QBC939膽管癌裸鼠模型療效進(jìn)行評(píng)估,將MVD、Ki67檢測(cè)結(jié)果進(jìn)行對(duì)比,探討利用MR-DWI檢查在評(píng)估光動(dòng)力在治療人QBC939膽管癌皮下荷瘤裸鼠模型療效方面的應(yīng)用價(jià)值、淺談金絲桃素PDT治療QBC939膽管癌的機(jī)制,觀察以金絲桃素作為光敏劑進(jìn)行PDT治療的近期療效,從而為3.0TMRI評(píng)估光動(dòng)力治療膽管癌療效提供重要臨床依據(jù)。材料與方法:利用人QBC939膽管癌細(xì)胞株建立30只皮下移植瘤裸鼠模型,并將其平均分為A(對(duì)照組)、B(金絲桃素PDT組)兩組,處理前后進(jìn)行MRI和DWI掃描,MR序列包括軸位、矢狀位、冠狀位tirmT2WI序列、軸位、矢狀位dark-fluid T1WI序列。DWI檢查采用diff-mddw序列行軸位DWI掃描,激勵(lì)次數(shù)(NXE)=1,b值分別為:0/mm2-300s/mm2,0/mm2-700s/mm2,得到兩組 b 值下 A、B 兩組處理前后人 QBC939膽管癌裸鼠皮下移植瘤模型腫瘤病灶的DWI圖及相應(yīng)ADC圖,篩選出最佳ADC圖,測(cè)量ADC值。A、B兩組分別注射勝生理鹽水、金絲桃素,然后進(jìn)行光照處理,A組實(shí)驗(yàn)鼠在完成第二次影像學(xué)檢查后同B組一起處死,兩組荷瘤裸鼠病灶進(jìn)行常規(guī)HE染色切片,并進(jìn)行免疫組化CD34染色計(jì)數(shù)微血管密度MVD和Ki67染色。結(jié)果:QBC939膽管癌病灶A(yù)DC值與Ki67呈負(fù)相關(guān),P0.05結(jié)果具有統(tǒng)計(jì)學(xué)意義;與MVD相關(guān)性較差,P0.05結(jié)果不具有統(tǒng)計(jì)學(xué)意義;治療后急性期內(nèi)治療組B組腫瘤體積為(3.11±0.78)cm3小于A組對(duì)照組體積(1.83±0.38)cm3。利用金絲桃素光動(dòng)力治療后B組膽管癌組織ADC值(985.39±36.99)×10-6mm2較A組ADC值(811.94±34.89)×10-6mm2明顯升高;KI67降低,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:利用3.0T MRI 4通道正交動(dòng)物線圈得到不同序列(T1WIT2WI和DWI)可以清晰顯示荷瘤鼠腫瘤組織形態(tài)、內(nèi)部信號(hào)、周圍組織局部受侵情況;ADC值與腫瘤Ki67有著良好相關(guān)性,可以在細(xì)胞水平上反映光動(dòng)力治療后人QBC939膽管癌裸鼠皮下移植瘤模型的腫瘤實(shí)性部分細(xì)胞增殖受限程度;DWI顯示光動(dòng)力治療在體膽管癌具有良好的療效,可以為光動(dòng)力治療膽管癌的臨床應(yīng)用提供重要幫助。
[Abstract]:Background and objective: cholangiocarcinoma (CC) is highly malignant, aggressive and occult. It is one of the most common and high mortality malignant tumors in China's biliary tract. Radical resection is the only cure for cholangiocarcinoma. However, patients undergoing radical resection on the bed are less than 10%. photodynamic ( Photodynamic therapy PDT) is a relatively mature treatment for cholangiocarcinoma abroad. However, the clinical application of hypericin as a photosensitizer for local treatment of cholangiocarcinoma is relatively small. The malignant degree of the bile duct cancer is high, the tumor angiogenesis, cell proliferation is an important biological behavior of the disease, which directly determines its malignant process. On the basis of the nude mice model of human QBC939 cholangiocarcinoma subcutaneous tumor, we use hypericin as photosensitizer to carry out photodynamic therapy, use magnetic resonance (MRI) T1WIT2WI, diffusion weighted imaging (DWI) to evaluate the effect of photodynamic treatment of nude mice model of QBC939 cholangiocarcinoma, compare the results of MVD, Ki67 detection, and explore the use of MR-DWI examination. To evaluate the application value of photodynamic in the treatment of nude mice model of QBC939 cholangiocarcinoma subcutaneous tumor, and to discuss the mechanism of hypericin PDT in the treatment of QBC939 cholangiocarcinoma, and observe the short-term effect of hypericin as a photosensitizer for the treatment of PDT, so as to provide an important clinical basis for the evaluation of the therapeutic effect of 3.0TMRI on the therapeutic effect of photodynamic therapy on cholangiocarcinoma. Materials and methods: the human QBC939 cholangiocarcinoma cell line was used to establish 30 nude mice models of subcutaneous transplantation tumor. The average was divided into A (control group) and B (hypericin PDT group). MRI and DWI scan were performed before and after treatment. The MR sequence included axial, sagittal, coronal tirmT2WI sequence, axis and sagittal dark-fluid T1WI sequence.DWI examination of diff-mddw Sequence row axis DWI scan, excitation frequency (NXE) =1, b value respectively: 0/mm2-300s/mm2,0/mm2-700s/mm2, obtained the DWI map and corresponding ADC map of the two groups of B values A, B two before and after treatment of the human QBC939 bile duct cancer nude mice subcutaneous tumor model. The best ADC diagram was screened, the two groups were injected with physiological saline and Hypericum respectively. The experimental mice in group A were executed with B after second times of imaging examination. The two groups of tumor bearing nude mice were stained with conventional HE staining and immunohistochemical CD34 staining was used to count the microvascular density MVD and Ki67 staining. The results showed that the ADC value of the QBC939 cholangiocarcinoma was negatively correlated with Ki67, and the P0.05 results were statistically significant. Significance; poor correlation with MVD, P0.05 results were not statistically significant; after treatment, the volume of tumor in group B was (3.11 + 0.78) cm3 less than that of group A (1.83 + 0.38) cm3. using hypericin (985.39 + 36.99) ADC (985.39 + 36.99) * 10-6mm2 (811.94 + 34.89) * 10-6mm2. The difference was statistically significant (P0.05). Conclusion: different sequences (T1WIT2WI and DWI) using the 3.0T MRI 4 channel orthogonal animal coils (T1WIT2WI and DWI) can clearly show the tumor tissue morphology, internal signal and local invasion of the surrounding tissues, and the ADC value has a good correlation with the tumor Ki67, which can reflect the light at the cell level. QBC939 cholangiocarcinoma in nude mice after dynamic treatment of nude mice with subcutaneous transplantation tumor model of tumor real part of cell proliferation limitation, DWI showed that photodynamic therapy has good therapeutic effect in body cholangiocarcinoma, and can provide important help for the clinical application of photodynamic treatment of cholangiocarcinoma.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.8;R445.2
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本文編號(hào)：1974016