本文關(guān)鍵詞： 神經(jīng)膠質(zhì)瘤 雙氫青蒿素 Notch信號通路 NICD-1 增殖和凋亡　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的探討雙氫青蒿素(dihydroartemisinine,DHA)對人腦膠質(zhì)瘤增殖和凋亡的影響及機(jī)制。方法1.人膠質(zhì)瘤U251細(xì)胞株傳代培養(yǎng),設(shè)置空白對照組、DMSO組、DAPT組和DHA組(10、20、40、80μmol/L),應(yīng)用CCK-8和FCM法檢測細(xì)胞增殖、周期及早期凋亡,Western blot檢測Notch1的胞內(nèi)區(qū)域(NICD-1)及其下游靶蛋白Hes1的表達(dá)水平;2.建立裸鼠皮下膠質(zhì)瘤模型(n=20),按隨機(jī)數(shù)表將其隨機(jī)分為DMSO對照組、DAPT組、DHA治療組(50、100mg/kg),每組5只,根據(jù)時間體積曲線計(jì)算各組抑瘤率,免疫組化法檢測裸鼠皮下移植瘤組織中NICD-1表達(dá)水平變化。結(jié)果1.與空白對照組和DMSO組相比,DHA組U251細(xì)胞增殖率顯著下降,G1期細(xì)胞所占百分比顯著上升,S期細(xì)胞所占百分比顯著下降,早期凋亡率顯著上升(P0.05),NICD-1及Hes1蛋白表達(dá)水平顯著低于空白對照組(P0.05),均呈濃度依賴關(guān)系;2.DHA各治療組的裸鼠皮下移植瘤生長速率及移植瘤組織內(nèi)NICD-1表達(dá)顯著低于DMSO對照組(P0.05)。結(jié)論DHA有效抑制人神經(jīng)膠質(zhì)瘤細(xì)胞增殖,促進(jìn)其凋亡;其作用機(jī)制可能與通過下調(diào)NICD-1的表達(dá),抑制Notch信號通路有關(guān)。
[Abstract]:Objective to study dihydroartemisinine dihydroartemisinine. The effect and mechanism of DHA on the proliferation and apoptosis of human glioma. 1. Human glioma U251 cell line was subcultured, and the blank control group was set up as DMSO group and DHA group. 2. CCK-8 and FCM were used to detect cell proliferation, cell cycle and early apoptosis. Western blot was used to detect the expression of NICD-1 in the intracellular region of Notch1 and its downstream target protein Hes1. 2. The model of subcutaneous glioma in nude mice was established and randomly divided into DMSO control group (n = 5) and DAPT group (n = 5). According to the time volume curve to calculate the tumor inhibition rate, immunohistochemical method to detect the expression of NICD-1 in nude mice subcutaneous transplanted tumor tissue. Results 1.Compared with the blank control group and DMSO group. 2. In DHA group, the proliferation rate of U251 cells decreased significantly; the percentage of cells in G 1 phase increased significantly; the percentage of S phase cells decreased significantly, and the early apoptosis rate increased significantly (P 0.05). The expression levels of NICD-1 and Hes1 protein were significantly lower than those of the control group (P 0.05), both in a concentration-dependent manner. 2. The growth rate of subcutaneous transplanted tumor and the expression of NICD-1 in xenografts of nude mice in DHA treatment group were significantly lower than those in DMSO control group (P0.05). Conclusion DHA can effectively inhibit the proliferation of human glioma cells. Promoting apoptosis; The mechanism may be related to the inhibition of Notch signaling pathway by down-regulating the expression of NICD-1.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.41

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