發(fā)布時間：2019-04-11 10:18

【摘要】：目的探討苦參堿(MAT)對阿霉素(ADM)損傷足細胞的干預作用及哺乳動物雷帕霉素靶蛋白(mTOR)在此過程中的表達。 方法永生化小鼠足細胞分化成熟后,用lumol/L的ADM損傷小鼠足細胞24小時造模,以不同濃度的MAT干預,檢測足細胞活力、足細胞凋亡比例、足細胞結蛋白(Desmin)和mTOR的表達,分析不同濃度的MAT對ADM損傷足細胞的干預效果,并探討mTOR在MAT干預過程中的作用。 結果1.MAT的干預減輕了ADM對足細胞的損傷。予ADM造模后,與對照組相比,足細胞活性下降(P0.001)、足細胞凋亡比例增加(P0.001)、損傷標志分子Desmin表達增多(P=0.002)；給予10、20、40ug/ml MAT干預后,相對于造模組,足細胞活性增加(均P0.05),足細胞凋亡減少(P0.05)Desmin表達下降(P0.05)。2.mTOR信號通路參與了ADM損傷和MAT干預足細胞這一機理。足細胞受損后,Western Blotting檢測提示：在蛋白水平,mTOR和磷酸化mTOR表達均下降(P0.05)；給予10、20、40ug/ml MAT干預,mTOR. p-mROR表達較造模組增加(P0.05)。RT-PCR提示：在基因水平,ADM損傷足細胞mTOR下游靶分子S6K1和4EBP1mRNA表達下降(P=0.071),予10、20、40ug/ml MAT干預后,S6K1和4EBP1mRNA表達均回升(P0.05)。 結論1.10～40ug/ml的MAT對ADM損傷足細胞有保護作用；2.保護機制可能與mTOR信號通路有關。
[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.
【學位授予單位】：蘭州大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R726.9;R285

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