本文選題：自噬 + 膠質(zhì)瘤��； 參考：《吉林大學(xué)》2014年碩士論文

【摘要】：膠質(zhì)瘤是最常見的腦原發(fā)性腫瘤[1]，占顱內(nèi)原發(fā)腫瘤的35.26%～60.96%[2]。顱內(nèi)膠質(zhì)瘤會(huì)逐漸向四周擴(kuò)散生長(zhǎng)，每個(gè)位置都存在獨(dú)特的病理特征以及不同的惡性程度。臨床可采用手術(shù)、放射、化學(xué)藥物、生物及其他方式開展治療，但該病的腫瘤細(xì)胞具有很強(qiáng)的增殖能力，即便腫瘤有效的全切后，患者的預(yù)后效果仍然很難讓人滿意[3]。國(guó)內(nèi)外對(duì)該疾病的研究成果較多，文獻(xiàn)多以手術(shù)、放療、藥物、生物等聯(lián)合的治療方式為主，針對(duì)疾病的病理特性提出針對(duì)性的綜合治療方案，但多數(shù)研究?jī)H能夠保證患者的短期生存時(shí)間，，無法起到有效的根治作用，該病已逐漸成為世界醫(yī)學(xué)范圍內(nèi)公認(rèn)的治療難題。 因此，我們?cè)谝酝芯抗ぷ鞯幕A(chǔ)上，采用體外培養(yǎng)膠質(zhì)瘤細(xì)胞等方法，探討了自噬在膠質(zhì)瘤細(xì)胞耐受替莫唑胺治療過程中的作用. 實(shí)驗(yàn)?zāi)康?探討自噬對(duì)膠質(zhì)瘤細(xì)胞耐受替莫唑胺治療中的作用 拮抗自噬對(duì)替莫唑胺治療膠質(zhì)瘤細(xì)胞的影響及機(jī)制 實(shí)驗(yàn)方法: 1、通過MTT法檢測(cè)TMZ誘導(dǎo)膠質(zhì)瘤細(xì)胞SHG44死亡情況，并探索3-MA對(duì)該種細(xì)胞死亡的作用。 2、通過流式細(xì)胞術(shù)進(jìn)一步檢測(cè)TMZ誘導(dǎo)膠質(zhì)瘤細(xì)胞SHG44的凋亡。 3、通過吖啶橙染色及MDC染色證明TMZ誘導(dǎo)膠質(zhì)瘤細(xì)胞SHG44死亡的過程中伴隨強(qiáng)烈的自噬產(chǎn)生。 4、通過透射電鏡直接觀察TMZ誘導(dǎo)膠質(zhì)瘤細(xì)胞產(chǎn)生的自噬情況。 實(shí)驗(yàn)結(jié)果: MTT實(shí)驗(yàn)結(jié)果證實(shí)：與control組比較，TMZ90μmol/L組、TMZ90μmol/L+3-MA組細(xì)胞存活率明顯降低（p0.05），TMZ90μmol/L+3-MA組與TMZ90μmol/L組比較，細(xì)胞存活率降低有統(tǒng)計(jì)學(xué)差異（p0.05）。流式細(xì)胞術(shù)實(shí)驗(yàn)結(jié)果進(jìn)一步證實(shí)了上述結(jié)果。吖啶橙染色實(shí)驗(yàn)結(jié)果顯示：TMZ90μmol/L組， TMZ90μmol/L+3-MA組與Control組及Control+3-MA組相比，胞漿內(nèi)紅色顆粒明顯增多，比較證實(shí)TMZ90μmol/L+3-MA組比TMZ90μmol/L組，胞漿內(nèi)紅色顆粒明顯減少。MDC染色實(shí)驗(yàn)結(jié)果顯示：TMZ90μmol/L組， TMZ90μmol/L+3-MA組與Control組及Control+3-MA組相比，胞漿內(nèi)綠色顆粒明顯增多，并且TMZ90μmol/L+3-MA組與TMZ90μmol/L組比較，胞漿內(nèi)綠色顆粒明顯減少，熒光強(qiáng)度明顯降低。 實(shí)驗(yàn)結(jié)論: 1、TMZ可降低腫瘤細(xì)胞生存率，同時(shí)產(chǎn)生保護(hù)性自噬，導(dǎo)致膠質(zhì)瘤細(xì)胞耐藥。 2、抑制自噬能夠提高TMZ對(duì)膠質(zhì)瘤細(xì)胞的殺傷作用。
[Abstract]:Glioma is the most common primary brain tumor, accounting for 35.2696% of primary intracranial tumors. Intracranial gliomas gradually proliferate and grow around each location with unique pathological features and different degrees of malignancy. Surgery, radiation, chemotherapeutic, biological and other methods can be used in clinical treatment, but the tumor cells of the disease have strong proliferative ability, even after the effective total resection of the tumor, the prognosis of the patients is still very difficult to be satisfactory [3]. There are many research results on the disease at home and abroad. The literature is mainly combined with surgery, radiotherapy, medicine, biology and so on. According to the pathological characteristics of the disease, a targeted comprehensive treatment scheme is put forward. However, most studies can only guarantee the short life time of the patients, and can not play an effective role in radical cure. The disease has gradually become a medical problem in the world. Therefore, on the basis of previous studies, we investigated the role of autophagy in the treatment of glioma cell tolerance to temozolamide by means of in vitro culture of glioma cells. Objective: to investigate the role of autophagy in the treatment of glioma cell tolerance to temozolamide. Effect of antagonistic autophagy on the treatment of glioma cells with temozolamide and its mechanism Experimental methods: 1. TMZ induced SHG44 death in glioma cells was detected by MTT assay, and the effect of 3-MA on SHG44 cell death was explored. 2. The apoptosis of SHG44 cells induced by TMZ was further detected by flow cytometry. 3. Acridine orange staining and MDC staining showed that TMZ induced SHG44 death in glioma cells with strong autophagy. 4. The autophagy of glioma cells induced by TMZ was observed by transmission electron microscope. Experimental results: The results of MTT assay showed that compared with control group, the cell survival rate of TMZ90 渭 mol/L 3-MA group was significantly lower than that of TMZ90 渭 mol/L group. The cell survival rate of TMZ90 渭 mol/L 3-MA group was significantly lower than that of TMZ90 渭 mol/L group. The results of flow cytometry further confirmed the above results. The results of acridine orange staining showed that the number of red granules in the cytoplasm of the TMZ90 渭 mol/L 3-MA group was significantly higher than that of the Control group and Control 3-MA group. The results of acridine orange staining showed that the red granules in the cytoplasm of the TMZ90 渭 mol/L 3-MA group were significantly higher than that of the TMZ90 渭 mol/L group. The results of cytoplasmic red granules reduction. MDC staining showed that the green granules in the cytoplasm were significantly increased in the TMZ90 渭 mol/L 3-MA group compared with the Control group and the Control 3-MA group, and the green granules in the cytoplasm in the TMZ90 渭 mol/L 3-MA group were significantly lower than those in the TMZ90 渭 mol/L group, and in the TMZ90 渭 mol/L 3-MA group compared with the Control and Control 3-MA groups, the number of green granules in the cytoplasm was significantly lower than that in the TMZ90 渭 mol/L group. The fluorescence intensity decreased obviously. The experimental conclusions are as follows: TMZ can reduce the survival rate of tumor cells and produce protective autophagy, leading to drug resistance of glioma cells. 2. Inhibition of autophagy can enhance the killing effect of TMZ on glioma cells.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.41

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