發(fā)布時(shí)間：2018-04-29 18:10

  本文選題：人腦膠質(zhì)瘤 + 細(xì)胞凋亡��； 參考：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：人腦膠質(zhì)細(xì)胞瘤腦簡(jiǎn)稱膠質(zhì)瘤,是人類中樞神經(jīng)系統(tǒng)中最常見(jiàn)的惡性腫瘤之一。由于它呈侵襲性生長(zhǎng)，使得臨床治療困難，是導(dǎo)致病人死亡的主要原因。我國(guó)是膠質(zhì)瘤的高發(fā)國(guó)家，每年的發(fā)病人數(shù)和因膠質(zhì)瘤而死亡人數(shù)都位居各種惡性腫瘤的前列，由于它的侵襲性生長(zhǎng)，在治療上成為一個(gè)世界性難題。腫瘤的發(fā)生和發(fā)展是多因素、多基因、綜合作用的結(jié)果。膠質(zhì)瘤是顱內(nèi)主要的原發(fā)性腫瘤[1]，與多種凋亡基因，，原癌基因，抑癌基因與膠質(zhì)瘤的發(fā)生有關(guān)，這些基因作用在腫瘤細(xì)胞增殖和凋亡的不同環(huán)節(jié)，凋亡抑制或平衡失調(diào)，可導(dǎo)致腫瘤細(xì)胞過(guò)度增殖，決定腫瘤的生長(zhǎng)、轉(zhuǎn)移和預(yù)后。目前研究證實(shí)，在多種腫瘤的發(fā)生、發(fā)展，侵襲和轉(zhuǎn)移的機(jī)制中，許多細(xì)胞粘附分子和水解蛋白酶發(fā)揮重要作用，其作用機(jī)制也陸續(xù)被闡明，但與膠質(zhì)瘤的關(guān)系報(bào)道并不多，因此，關(guān)于膠質(zhì)瘤的發(fā)生、發(fā)展，浸潤(rùn)生長(zhǎng)等機(jī)制的研究有必要從分子水平著手。 細(xì)胞凋亡是細(xì)胞在各種死亡信號(hào)刺激后發(fā)生的一系列瀑布式的主動(dòng)性死亡過(guò)程，受多種基因調(diào)控。與caspase3家族和bcl2家族密切相關(guān)。腫瘤細(xì)胞的凋亡，增殖和抗凋亡的相互作用，決定腫瘤生物學(xué)行為的惡性進(jìn)展程度。目前研究較多的是caspase3與bcl2在消化道腫瘤（如胃癌、肝癌、結(jié)腸癌、胰腺癌等）和泌尿生殖系腫瘤（如乳腺癌、子宮癌、卵巢癌、腎癌、膀胱癌等）中的表達(dá)，而在腦膠質(zhì)瘤中的表達(dá)研究還比較少。腦膠質(zhì)瘤為常見(jiàn)的顱內(nèi)腫瘤,深入研究caspase3和bcl2在腦膠質(zhì)瘤中的表達(dá)及其與腦膠質(zhì)瘤臨床病理分型之間的關(guān)系,可能成為腦膠質(zhì)瘤的診斷、預(yù)后、治療的一條新途徑。本課題通過(guò)檢測(cè)caspase3，Bcl2在不同級(jí)別腦膠質(zhì)瘤中的表達(dá)以探討caspase3，Bcl2對(duì)腦膠質(zhì)瘤發(fā)生、發(fā)展及預(yù)后的意義。 方法：收集2012年12月至2013年4月于河北醫(yī)科大學(xué)第二醫(yī)院神經(jīng)外科手術(shù)切除的人腦膠質(zhì)瘤標(biāo)本60例。按照WHO2007年中樞神經(jīng)系統(tǒng)腫瘤分類，Ⅰ~Ⅱ級(jí)為低級(jí)別膠質(zhì)瘤，共23例； Ⅲ~Ⅳ級(jí)為高級(jí)別膠質(zhì)瘤，共37例，均有完整病歷資料并經(jīng)本院病理科證實(shí)。另取11例因外傷或者腦出血而進(jìn)行的顱內(nèi)減壓的正常腦組織標(biāo)本作為對(duì)照。膠質(zhì)瘤患者于手術(shù)前均未進(jìn)行放化療等任何抗腫瘤治療。所有標(biāo)本均在手術(shù)切下組織后立即取材，分別于10%的福爾馬林固定及液氮保存，采用免疫組織化學(xué)法IHC和RT-PCR分別檢測(cè)Bcl2、Caspase3在膠質(zhì)瘤中蛋白水平和mRNA水平的表達(dá)情況。實(shí)驗(yàn)結(jié)果數(shù)據(jù)用SPSS16.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果： 1IHC結(jié)果顯示:Bcl2在正常腦組織、低、高級(jí)別膠質(zhì)瘤組表達(dá)陽(yáng)性率分別為9%、78%、100%；Caspase3表達(dá)陽(yáng)性率分別為0%、100%、84%。Bcl2、Caspase3在三組間表達(dá)有顯著性統(tǒng)計(jì)學(xué)差異（P=0.000），組間兩兩比較均有顯著性統(tǒng)計(jì)學(xué)差異（P＜0.05），隨腫瘤惡性程度增高，Bcl2表達(dá)量增高，Caspase3表達(dá)量減少。Bcl2和Caspase3在正常腦組織、低、高級(jí)別膠質(zhì)瘤三組中表達(dá)呈負(fù)相關(guān)（r=-0.814，P=0.000），在其余組間表達(dá)未見(jiàn)相關(guān)關(guān)系，可能與樣本量少有關(guān)。 2RT-PCR結(jié)果顯示：Bcl2、Caspase3在正常腦組織、低、高級(jí)別膠質(zhì)瘤三組間表達(dá)有顯著性統(tǒng)計(jì)學(xué)差異（P＜0.05），組間兩兩比較均有顯著性統(tǒng)計(jì)學(xué)差異（P＜0.05），隨腫瘤惡性程度增高，Bcl2表達(dá)量增高，Caspase3表達(dá)量減少。并且Bcl2和Caspase3在正常腦組織、低、高級(jí)別膠質(zhì)瘤三組中表達(dá)呈負(fù)相關(guān)（r=-0.254, P=0.032），在腫瘤組（包括低、高級(jí)別膠質(zhì)瘤）表達(dá)也呈負(fù)相關(guān)（r=-0.48，P=0.000），在其余組中按P＜0.05檢驗(yàn)水準(zhǔn)下未見(jiàn)相關(guān)性。 結(jié)論： 1Bcl2在正常腦組織、低、高級(jí)別膠質(zhì)瘤組三組間及組間兩兩比較表達(dá)有顯著性統(tǒng)計(jì)學(xué)差異，隨腫瘤惡性程度增高，Bcl2表達(dá)量增高，在高級(jí)別膠質(zhì)瘤中表達(dá)水平最高，與膠質(zhì)瘤的惡性程度相關(guān)。 2Caspase3在正常腦組織、低、高級(jí)別膠質(zhì)瘤組三組間及組間兩兩比較表達(dá)有顯著性統(tǒng)計(jì)學(xué)差異，隨腫瘤惡性程度增高，Caspase3表達(dá)量減少，在低級(jí)別膠質(zhì)瘤中表達(dá)水平最高，與膠質(zhì)瘤的惡性程度相關(guān)。 3Caspase3的表達(dá)下調(diào)與膠質(zhì)瘤的惡性進(jìn)展關(guān)系密切，Bcl2在膠質(zhì)瘤的發(fā)生、發(fā)展過(guò)程中起重要作用。Caspase3和Bcl2可能成為膠質(zhì)瘤預(yù)后判斷的潛在指標(biāo)。 4Caspase3和Bcl2在膠質(zhì)瘤中的表達(dá)存在相關(guān)性，隨著Caspase3的表達(dá)下調(diào)，Bcl2的表達(dá)上調(diào)。
[Abstract]:Objective: human glioblastoma, called glioma, is one of the most common malignant tumors in the human central nervous system. It is a major cause of death because of its invasive growth and difficult clinical treatment. China is a country with high incidence of glioma, and the number of patients and the number of deaths due to glioma are all in the place of each year. The forefront of malignant tumors, due to its invasive growth, has become a worldwide problem in the treatment of cancer. The occurrence and development of tumor are the results of multiple factors, multiple genes and comprehensive effects. Glioma is the primary primary tumor of the intracranial [1], which is related to the occurrence of a variety of apoptotic genes, proto oncogenes, tumor suppressor genes and glioma. In the different links of tumor cell proliferation and apoptosis, apoptosis inhibition or imbalance can lead to overproliferation of tumor cells and determine tumor growth, metastasis and prognosis. The mechanism has been clarified, but there are few reports on the relationship between glioma and glioma. Therefore, it is necessary to study the mechanism of the occurrence, development and infiltration of glioma from the molecular level.
Cell apoptosis is a series of waterfall active death processes that occur after various death signals, which are regulated by a variety of genes. It is closely related to the Caspase3 family and the BCL2 family. The apoptosis, proliferation and anti apoptosis interaction of tumor cells determine the malignant progression of tumor biology. At present, more research is on CA. Spase3 and BCL2 are expressed in digestive tract tumors (such as gastric cancer, liver cancer, colon cancer, pancreatic cancer, etc.) and urogenital tumors (such as breast, uterine, ovarian, renal, bladder cancer), while the expression in glioma is still less. Glioma is a common intracranial tumor, and Caspase3 and BCL2 are deeply studied in glioma. The relationship between the expression and the clinicopathological classification of glioma may be a new approach for the diagnosis, prognosis and treatment of glioma. This topic is to explore the significance of Caspase3 and Bcl2 to the occurrence, development and prognosis of glioma by detecting the expression of Caspase3 and Bcl2 in different levels of glioma.
Methods: 60 cases of glioma resection in Department of Neurosurgery, Second Hospital of Hebei Medical University from December 2012 to April 2013, were collected in the Department of Neurosurgery, Second Hospital of Hebei Medical University. According to the classification of central nervous system tumor, grade I ~ II was low grade glioma in 23 cases, grade III ~ IV was high grade glioma, a total of 37 cases had complete medical records and had been treated by our hospital. The normal brain tissue specimens from 11 cases of intracranial decompression due to trauma or cerebral hemorrhage were taken as control. The patients with glioma were not treated with radiotherapy and chemotherapy before operation. All specimens were harvested immediately after surgical removal of the tissue, respectively, in 10% of the formalin fixation and the preservation of liquid nitrogen, using the immune group. The expression of protein level and mRNA level of Bcl2 and Caspase3 in glioma was detected by IHC and RT-PCR, respectively. The results of the experimental data were statistically analyzed by SPSS16.0 software.
Result錛

本文編號(hào)：1821015