Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments
Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments
复制标题
ERK信号通路抑制剂PD98059在长期体内实验中的应用
DOI：
10.4238/2015.december.23.20
复制
发表时间：
2015-01-01
影响因子：
0.4
通讯作者：
Tang, Y. P.
中科院分区：
文献类型：
--
作者：
Chen, X. Y.;Cai, H. Z.;Tang, Y. P.
本研究的目的是探索ERK信号通路抑制剂PD 98059（PD）用于长期体内实验的方法。将40只健康新西兰兔随机分为空白对照组、模型对照组、PD低剂量组、PD高剂量组、PD空白组、二甲基亚砜（DMSO）对照组、DMSO空白组和阳性对照组。在4周的过程中对每个实验组进行相应的处理，之后，测量心肌组织中的总ERK 1/2和ERK 5蛋白水平、蛋白磷酸化和基因表达。阿霉素治疗组ERK 1/2和ERK 5磷酸化水平与对照组相比有显著性差异（P < 0.05）。与模型对照组相比，PD高剂量组磷酸化ERK 1/2和磷酸化ERK 5的变化最小（P < 0.05）。4周后各组心肌细胞ERK 1/2和ERK 5的总蛋白和mRNA水平差异无统计学意义（P > 0.05）。连续静脉注射PD 98059显著降低ERK 1/2和ERK 5的磷酸化。总之，阿霉素诱导的心肌病和ERK信号异常可能构成一个有价值的模型，用于长期的实验。这些方法可为相关的长期体内研究提供理论依据。
The aim of this study was to explore methods by which the ERK signaling pathway inhibitor PD98059 (PD) could be used in long-term in vivo experiments. Forty healthy New Zealand rabbits were randomly divided into blank control, model control, PD low-dose, PD high-dose, PD blank, dimethyl sulfoxide (DMSO) control, DMSO blank, and positive control groups. The corresponding treatments were administered to each experimental group over the course of four weeks, after which, total ERK1/2 and ERK5 protein levels, protein phosphorylation, and gene expression were measured in myocardial tissues. Treatment of rabbits with Adriamycin (doxorubicin) resulted in the significant overall differences in ERK1/2 and ERK5 phosphorylation (P < 0.05). Compared with the model control group, changes in phosphorylated ERK1/2 and phosphorylated ERK5 were lowest in the PD high-dose group (P < 0.05). No significant differences in total protein and mRNA levels of myocardial ERK1/2 and ERK5 were detected between the groups after four weeks (P > 0.05). Continuous intravenous injection of PD98059 significantly reduced phosphorylation of ERK1/2 and that of ERK5. In conclusion, Adriamycin-induced myocardiopathy and abnormal ERK signaling might constitute a valuable model foruse in long-term experiments. These methods may provide a theoretical basis for related in vivo studies of long duration.