本文選題：姜黃素納米粒制劑 + 髓母細(xì)胞瘤��； 參考：《重慶醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：髓母細(xì)胞瘤（Medulloblastoma，，MB）是兒童常見惡性程度極高的中樞神經(jīng)系統(tǒng)腫瘤之一，臨床上以手術(shù)治療為主，但療效欠佳，病死率高，預(yù)后差。已有報道指出姜黃素(Curcumin, Cur)對髓母細(xì)胞瘤細(xì)胞有較強(qiáng)的抑制效果且基本無毒副作用。但由于姜黃素水溶性低，穩(wěn)定性差，發(fā)揮藥效所需用量大的缺點(diǎn)阻礙了其在臨床的應(yīng)用和推廣。藥學(xué)研究證實(shí)姜黃素納米粒制劑（Curcumin nanoparticles，Cur-N）較單純姜黃素具有更高生物利用度，更好穩(wěn)定性而用藥量更低，但其對髓母細(xì)胞瘤的生物學(xué)活性是否有所增強(qiáng)尚不明確。本文主要研究姜黃素固體脂質(zhì)納米粒制劑對髓母細(xì)胞瘤Daoy細(xì)胞株的抑制效應(yīng)，并將其與單純姜黃素進(jìn)行對比，以明確其是否具有更高的藥效和安全性。 方法：體外培養(yǎng)髓母細(xì)胞瘤Daoy細(xì)胞株并分為4組給予不同的干預(yù)措施，分別為空白對照組(不加任何處理的Daoy細(xì)胞株)，原藥組（加入單純姜黃素處理），制劑對照組（加入空白納米微粒載體溶劑處理），制劑組（加入姜黃素納米粒制劑處理），藥物濃度梯度分別為2.5、5.0、10.0、20.0、40.0μM/L，處理時相點(diǎn)為24h、48h、72h,處理后用MTT檢測髓母瘤細(xì)胞增殖情況的變化；劃痕實(shí)驗(yàn)和Transwell小室模型檢測細(xì)胞遷移，流式細(xì)胞術(shù)檢測細(xì)胞凋亡率、細(xì)胞周期和細(xì)胞內(nèi)鈣離子濃度變化。 結(jié)果：MTT、劃痕實(shí)驗(yàn)和Transwell小室模型顯示：原藥組（加入單純姜黃素處理）及制劑組（加入姜黃素納米粒復(fù)合制劑處理）在不同濃度下作用不同時間對細(xì)胞的增殖、遷移有不同程度的抑制效應(yīng)，在作用48h時對細(xì)胞增殖的抑制效應(yīng)最明顯，IC50分別為37.3μM/L、5.2μM/L，與對照組相比差異存在統(tǒng)計學(xué)意義（P0.05）；流式細(xì)胞術(shù)顯示：原藥組及制劑組對Daoy細(xì)胞有明顯的抑制效應(yīng)，可不同程度促進(jìn)Daoy細(xì)胞的凋亡（P0.05），使細(xì)胞內(nèi)鈣離子濃度明顯升高（P0.05）；抑制效應(yīng)表現(xiàn)在細(xì)胞周期上可見到更多細(xì)胞停留在S/G2期（P0.05），甚至出現(xiàn)G2/M期阻滯。其中全部實(shí)驗(yàn)均顯示制劑組較原藥組的抑制效應(yīng)明顯增強(qiáng)，差異具有統(tǒng)計學(xué)意義（P0.05）；制劑對照組（加入空白納米微粒載體溶劑處理）和空白對照組(不加任何處理的Daoy細(xì)胞株)相比對細(xì)胞的影響無明顯變化，差異不具有統(tǒng)計學(xué)意義（P0.05）。 結(jié)論：姜黃素納米粒制劑明顯提高了姜黃素對髓母細(xì)胞瘤Daoy細(xì)胞的抑制效應(yīng)，較姜黃素能更大程度的促進(jìn)細(xì)胞凋亡，抑制其增殖和遷移，具有更好的抗腫瘤生物學(xué)活性和安全性，也許今后能成為姜黃素的替代品更廣泛的應(yīng)用在髓母細(xì)胞瘤的臨床治療上。
[Abstract]:Objective: Medulloblastomaomb (Medulloblastomaomb) is one of the most common malignant central nervous system tumors in children. The main clinical treatment is surgical treatment, but the curative effect is poor, the fatality rate is high, and the prognosis is poor.It has been reported that curcumin (Curcumin, Curcumin) has a strong inhibitory effect on medulloblastoma cells and has no toxic side effects.However, because curcumin has low water solubility and poor stability, the large dosage of curcumin hinders its clinical application and popularization.Pharmacological studies confirmed that curcumin nanoparticles-N- (Curcumin nanoparticles-N) had higher bioavailability, better stability and lower dosage than curcumin. However, it was not clear whether curcumin nanoparticles could enhance the biological activity of curcumin nanoparticles-N in medulloblastoma.The inhibitory effect of curcumin solid lipid nanoparticles on myeloblastoma Daoy cell line was studied and compared with curcumin alone to determine whether curcumin has higher efficacy and safety.Methods: Daoy cell lines of medulloblastoma were cultured in vitro and divided into 4 groups.Blank control group (Daoy cell line without any treatment), raw drug group (adding curcumin treatment alone), preparation control group (adding solvent treatment of blank nanoparticles carrier, preparation group (adding curcumin nanoparticles preparation)After treatment, the gradient of drug concentration was 2.5 ~ 5.0 ~ 10.0 ~ 20.0 渭 m / L, and the phase point was 24 h ~ 48 h ~ 72 h. After treatment, the proliferation of medulloblastoma cells was detected by MTT.Cell migration was detected by scratch assay and Transwell chamber model. Apoptosis rate, cell cycle and intracellular calcium concentration were detected by flow cytometry.Results the cell proliferation of the original drug group (treated with curcumin alone) and the preparation group (treated with curcumin nanoparticles compound) at different concentrations and at different time were found by the scratch test and Transwell chamber model.Migration has different inhibitory effects,The inhibitory effects of IC50 on cell proliferation were 37.3 渭 M / L ~ 5.2 渭 M / L, respectively, which were significantly different from those of the control group (P 0.05). Flow cytometry showed that the inhibitory effect on Daoy cells was obvious in the raw drug group and the preparation group.It could promote the apoptosis of Daoy cells to some extent and increase the intracellular calcium concentration of P0.05G, and the inhibitory effect was that more cells could stay in S/G2 phase P0.05N, and even G2 / M phase arrest could be seen in the cell cycle.All the experiments showed that the inhibitory effect of the preparation group was significantly stronger than that of the raw drug group.The difference was statistically significant (P 0.05), but there was no significant difference between the preparation control group (adding solvent treatment with blank nanoparticles carrier) and the blank control group (Daoy cell line without any treatment), and the difference was not statistically significant (P 0.05).Conclusion: curcumin nanoparticles can significantly increase the inhibitory effect of curcumin on Daoy cells of medulloblastoma. Curcumin can promote apoptosis, inhibit the proliferation and migration of myeloblastoma cells to a greater extent than curcumin.It may be used as a substitute for curcumin in clinical treatment of medulloblastoma.
【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】：2014
【分類號】：R739.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;崔永元 轉(zhuǎn)基因之戰(zhàn)[J];中華兒女;2014年01期

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