苦参碱对阿霉素损伤足细胞的干预作用及mTOR的表达
发布时间：2019-04-11 10:18
【摘要】：目的探讨苦参碱(MAT)对阿霉素(ADM)损伤足细胞的干预作用及哺乳动物雷帕霉素靶蛋白(mTOR)在此过程中的表达。 方法永生化小鼠足细胞分化成熟后,用lumol/L的ADM损伤小鼠足细胞24小时造模,以不同浓度的MAT干预,检测足细胞活力、足细胞凋亡比例、足细胞结蛋白(Desmin)和mTOR的表达,分析不同浓度的MAT对ADM损伤足细胞的干预效果,并探讨mTOR在MAT干预过程中的作用。 结果1.MAT的干预减轻了ADM对足细胞的损伤。予ADM造模后,与对照组相比,足细胞活性下降(P0.001)、足细胞凋亡比例增加(P0.001)、损伤标志分子Desmin表达增多(P=0.002)；给予10、20、40ug/ml MAT干预后,相对于造模组,足细胞活性增加(均P0.05),足细胞凋亡减少(P0.05)Desmin表达下降(P0.05)。2.mTOR信号通路参与了ADM损伤和MAT干预足细胞这一机理。足细胞受损后,Western Blotting检测提示：在蛋白水平,mTOR和磷酸化mTOR表达均下降(P0.05)；给予10、20、40ug/ml MAT干预,mTOR. p-mROR表达较造模组增加(P0.05)。RT-PCR提示：在基因水平,ADM损伤足细胞mTOR下游靶分子S6K1和4EBP1mRNA表达下降(P=0.071),予10、20、40ug/ml MAT干预后,S6K1和4EBP1mRNA表达均回升(P0.05)。 结论1.10～40ug/ml的MAT对ADM损伤足细胞有保护作用；2.保护机制可能与mTOR信号通路有关。
[Abstract]:Aim to investigate the effect of matrine (MAT) on doxorubicin (ADM)-induced podocyte injury and the expression of rapamycin target protein (mTOR) in mammals. Methods after podocyte differentiation and maturation in immortalized mice, podocytes were injured by ADM of lumol/L for 24 hours. The podocyte viability, podocyte apoptosis ratio, expression of podocyte desmin (Desmin) and mTOR were detected with different concentrations of MAT. To analyze the intervention effect of different concentrations of MAT on podocytes injured by ADM, and to explore the role of mTOR in the intervention of MAT. Results the intervention of 1.MAT alleviated the injury of podocyte induced by ADM. Compared with the control group, the podocyte activity decreased (P0.001), the percentage of podocyte apoptosis increased (P0.001), and the expression of Desmin, a marker of injury, increased (P0.001). After ADM was established, the podocyte activity was decreased (P0.001). Compared with the model group, the podocyte activity increased after the intervention of 10,20,40 ug / ml MAT (P0.05). The decrease of podocyte apoptosis (P0.05) decreased the expression of Desmin (P0.05). 2. MTOR signaling pathway was involved in the mechanism of ADM damage and MAT intervention in podocytes. The results of, Western Blotting showed that the expression of mTOR and phosphorylated mTOR in podocytes decreased at protein level (P0.05), and mTOR. was treated with 10, 20, 40 ug / ml MAT (P < 0.05). The expression of p-mROR was higher than that of the model group (P0.05). RT-PCR suggested that the expression of S6K1 and 4EBP1mRNA downstream target molecules of mTOR in podocytes injured by ADM decreased at gene level (P < 0. 071), and the expression of S6K1 and 4EBP1mRNA increased after 10, 20, 40 ug / ml MAT intervention (P0.05). Conclusion MAT of 1.10~40ug/ml has protective effect on podocytes damaged by ADM. The protective mechanism may be related to the mTOR signaling pathway.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R726.9;R285
本文编号：2456325
[Abstract]:Aim to investigate the effect of matrine (MAT) on doxorubicin (ADM)-induced podocyte injury and the expression of rapamycin target protein (mTOR) in mammals. Methods after podocyte differentiation and maturation in immortalized mice, podocytes were injured by ADM of lumol/L for 24 hours. The podocyte viability, podocyte apoptosis ratio, expression of podocyte desmin (Desmin) and mTOR were detected with different concentrations of MAT. To analyze the intervention effect of different concentrations of MAT on podocytes injured by ADM, and to explore the role of mTOR in the intervention of MAT. Results the intervention of 1.MAT alleviated the injury of podocyte induced by ADM. Compared with the control group, the podocyte activity decreased (P0.001), the percentage of podocyte apoptosis increased (P0.001), and the expression of Desmin, a marker of injury, increased (P0.001). After ADM was established, the podocyte activity was decreased (P0.001). Compared with the model group, the podocyte activity increased after the intervention of 10,20,40 ug / ml MAT (P0.05). The decrease of podocyte apoptosis (P0.05) decreased the expression of Desmin (P0.05). 2. MTOR signaling pathway was involved in the mechanism of ADM damage and MAT intervention in podocytes. The results of, Western Blotting showed that the expression of mTOR and phosphorylated mTOR in podocytes decreased at protein level (P0.05), and mTOR. was treated with 10, 20, 40 ug / ml MAT (P < 0.05). The expression of p-mROR was higher than that of the model group (P0.05). RT-PCR suggested that the expression of S6K1 and 4EBP1mRNA downstream target molecules of mTOR in podocytes injured by ADM decreased at gene level (P < 0. 071), and the expression of S6K1 and 4EBP1mRNA increased after 10, 20, 40 ug / ml MAT intervention (P0.05). Conclusion MAT of 1.10~40ug/ml has protective effect on podocytes damaged by ADM. The protective mechanism may be related to the mTOR signaling pathway.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R726.9;R285
【参考文献】
相关期刊论文 前9条
1 司维柯,高利宏,刘斌,陈安,李鹏,姚婕;苦参碱诱导人肝癌细胞分化、凋亡时对G_1细胞周期调节因子的调控[J];癌症;2001年08期
2 王艳芬,潘留兰,苑坤;氧化苦参碱的抗肝纤维化作用及其机制研究[J];中国医师杂志;2004年12期
3 伍严安,高春芳,王皓,黄超,孔宪涛;苦参碱抑制血小板衍生生长因子诱导的小鼠皮肤成纤维细胞增殖[J];第二军医大学学报;2000年08期
4 高健;梁耀军;金玉;李玉梅;李宇宁;;苦参碱对阿霉素诱导的肾小球硬化大鼠STAT3信号分子的影响[J];第四军医大学学报;2008年08期
5 夏洵;鹿玲;;足细胞转录因子和肾脏疾病研究进展[J];国际儿科学杂志;2006年06期
6 王新颖;Podocin与肾脏疾病[J];国外医学.泌尿系统分册;2004年01期
7 张友祥,张佳发,刘龙民;苦参及其有效成分治疗病毒性肝炎作用机理的研究进展[J];上海中医药大学学报;2001年02期
8 洪亦眉;陈朝红;;足细胞损伤的病因和发病机制[J];肾脏病与透析肾移植杂志;2009年01期
9 刘雅清;纪泽泉;;足细胞与足细胞病[J];肾脏病与透析肾移植杂志;2011年01期
，本文编号：2456325
本文链接：https://www.wllwen.com/yixuelunwen/eklw/2456325.html
最近更新
教材专著
