雷公藤内酯醇协同地塞米松诱导蕈样肉芽肿hut-102细胞凋亡及其机制

发布时间：2018-06-16 16:23

本文选题：Hut-102 + 雷公藤内酯醇　；参考：《重庆医科大学》2010年硕士论文

【摘要】： 蕈样肉芽肿(Mycosis fungoides,MF)是低度恶性皮肤T细胞淋巴瘤,易复发,预后差,早期外用糖皮质激素(glucocorticoid,GC)是控制疾病发展最常用的治疗方法之一。雷公藤内酯醇(Triptolide,TP)和糖皮质激素是皮肤科疾病治疗的常用药物,具有抗炎和免疫抑制等多种活性,两者联合治疗重症皮炎、湿疹、银屑病等炎症性疾病疗效较好。糖皮质激素通过激活细胞内受体(Glucocorticoid receptor,GR)发挥作用,两者之间的结合具有专一性。研究证实,糖皮质激素调节肿瘤细胞代谢的生物学效应需通过其受体介导,从而在转录及翻译水平调节相关基因的表达。Caspase酶在肿瘤细胞凋亡过程中具有不可忽视的作用,其中Caspase-3更是处于关键位置,多数细胞凋亡均通过Caspase-3介导的信号途径。本文以蕈样肉芽肿hut-102细胞为研究对象,探讨雷公藤联合地塞米松(dexamethasone,DEX)对该细胞体外增殖、凋亡的影响,进而分析两者是否具有交互效应及可能机制。研究方法:MTT法检测细胞存活率;流式细胞术检测细胞凋亡率;蛋白印迹法检测糖皮质激素受体GR和凋亡相关蛋白Caspase-3的表达。研究结果:①不同浓度雷公藤(6.25、12.5、25 nm/L)和地塞米松(10-7、10-6、10-5 mol/L)对hut-102细胞均有增殖抑制作用,与时间、浓度相关;12.5 nm/L雷公藤联合不同浓度地塞米松,与单药组相比,细胞抑制率明显升高(P㩳0.01),且随地塞米松浓度增大而升高。②雷公藤和地塞米松均能诱导该细胞凋亡,联合组凋亡率明显高于单药组(P㩳0.01),呈交互协同效应。③10-5 mol/L地塞米松作用hut-102细胞后,GR表达降低(P㩳0.05),联合组(12.5 nm/L雷公藤+10-5 mol/L地塞米松)较地塞米松组GR表达升高、Caspase-3激活增强(P㩳0.05)。研究结论:雷公藤联合地塞米松可明显抑制hut-102细胞增殖,增强诱导凋亡,具有交互协同效应,其作用机制可能与GR表达上调、Caspase-3激活增强有关。
[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.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.5

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