發(fā)布時(shí)間：2018-06-16 16:23

  本文選題：Hut-102 + 雷公藤內(nèi)酯醇　； 參考：《重慶醫(yī)科大學(xué)》2010年碩士論文

【摘要】： 蕈樣肉芽腫(Mycosis fungoides,MF)是低度惡性皮膚T細(xì)胞淋巴瘤,易復(fù)發(fā),預(yù)后差,早期外用糖皮質(zhì)激素(glucocorticoid,GC)是控制疾病發(fā)展最常用的治療方法之一。雷公藤內(nèi)酯醇(Triptolide,TP)和糖皮質(zhì)激素是皮膚科疾病治療的常用藥物,具有抗炎和免疫抑制等多種活性,兩者聯(lián)合治療重癥皮炎、濕疹、銀屑病等炎癥性疾病療效較好。 糖皮質(zhì)激素通過(guò)激活細(xì)胞內(nèi)受體(Glucocorticoid receptor,GR)發(fā)揮作用,兩者之間的結(jié)合具有專一性。研究證實(shí),糖皮質(zhì)激素調(diào)節(jié)腫瘤細(xì)胞代謝的生物學(xué)效應(yīng)需通過(guò)其受體介導(dǎo),從而在轉(zhuǎn)錄及翻譯水平調(diào)節(jié)相關(guān)基因的表達(dá)。Caspase酶在腫瘤細(xì)胞凋亡過(guò)程中具有不可忽視的作用,其中Caspase-3更是處于關(guān)鍵位置,多數(shù)細(xì)胞凋亡均通過(guò)Caspase-3介導(dǎo)的信號(hào)途徑。 本文以蕈樣肉芽腫hut-102細(xì)胞為研究對(duì)象,探討雷公藤聯(lián)合地塞米松(dexamethasone,DEX)對(duì)該細(xì)胞體外增殖、凋亡的影響,進(jìn)而分析兩者是否具有交互效應(yīng)及可能機(jī)制。 研究方法:MTT法檢測(cè)細(xì)胞存活率;流式細(xì)胞術(shù)檢測(cè)細(xì)胞凋亡率;蛋白印跡法檢測(cè)糖皮質(zhì)激素受體GR和凋亡相關(guān)蛋白Caspase-3的表達(dá)。 研究結(jié)果:①不同濃度雷公藤(6.25、12.5、25 nm/L)和地塞米松(10-7、10-6、10-5 mol/L)對(duì)hut-102細(xì)胞均有增殖抑制作用,與時(shí)間、濃度相關(guān);12.5 nm/L雷公藤聯(lián)合不同濃度地塞米松,與單藥組相比,細(xì)胞抑制率明顯升高(P㩳0.01),且隨地塞米松濃度增大而升高。②雷公藤和地塞米松均能誘導(dǎo)該細(xì)胞凋亡,聯(lián)合組凋亡率明顯高于單藥組(P㩳0.01),呈交互協(xié)同效應(yīng)。③10-5 mol/L地塞米松作用hut-102細(xì)胞后,GR表達(dá)降低(P㩳0.05),聯(lián)合組(12.5 nm/L雷公藤+10-5 mol/L地塞米松)較地塞米松組GR表達(dá)升高、Caspase-3激活增強(qiáng)(P㩳0.05)。 研究結(jié)論:雷公藤聯(lián)合地塞米松可明顯抑制hut-102細(xì)胞增殖,增強(qiáng)誘導(dǎo)凋亡,具有交互協(xié)同效應(yīng),其作用機(jī)制可能與GR表達(dá)上調(diào)、Caspase-3激活增強(qiáng)有關(guān)。
[Abstract]:Mycosis fungoides (MF) is a low-grade malignant cutaneous T-cell lymphoma, which is prone to recurrence and poor prognosis. Early use of glucocorticoid is one of the most commonly used treatments to control the development of the disease. Triptolide (TTP) and glucocorticoid are common drugs for dermatological treatment with anti-inflammatory and immunosuppressive activities. The combined treatment of severe dermatitis eczema psoriasis and other inflammatory diseases is effective. Glucocorticoids play a role by activating intracellular receptor Glucocorticoid receptor (GRG), and the binding between them is specific. It has been demonstrated that the biological effects of glucocorticoid on the metabolism of tumor cells need to be mediated by their receptors, which may play an important role in regulating the expression of related genes at the transcriptional and translation levels in the process of tumor cell apoptosis. Caspase-3 is at the key position, and most of the cell apoptosis is mediated by Caspase-3 signaling pathway. The effects of Tripterygium wilfordii and dexamethasone on the proliferation and apoptosis of hut-102 cells were studied in vitro. Methods the cell survival rate was detected by MTT assay, the apoptosis rate by flow cytometry and the expression of glucocorticoid receptor gr and apoptosis-related protein Caspase-3 by Western blotting. The results showed that different concentrations of tripterygium wilfordii and dexamethasone 10-7 + 10-6 + 10-5 mol / L) inhibited the proliferation of hut-102 cells at different concentrations of 6.25 Nm / L and 12.5 nm / L, respectively, compared with the single drug group, and the effect was related to the time and concentration of tripterygium wilfordii and dexamethasone at different concentrations. The cell inhibition rate was significantly increased with the increase of dexamethasone concentration and the apoptosis was induced by both tripterygium wilfordii and dexamethasone. The apoptotic rate in the combined group was significantly higher than that in the single drug group. The expression of gr in hut-102 cells decreased after the treatment of dexamethasone with 310-5 mol / L dexamethasone, and the expression of Caspase-3 was increased in the combined group (12.5 nm / L Tripterygium wilfordii 10-5 mol / L dexamethasone) compared with that in the dexamethasone group. Conclusion: Tripterygium wilfordii combined with dexamethasone can significantly inhibit the proliferation of hut-102 cells and enhance the induction of apoptosis, which may be related to the up-regulation of gr expression and the activation of Caspase-3.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R739.5

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