p38MAPK 在大鼠下肢动脉缺血再灌注损伤模型中的作用。
The involvement of p38MAPK in the rat model of lower-extremity arterial ischemia-reperfusion injury.
机构信息
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5659-5664. doi: 10.26355/eurrev_201809_15833.
OBJECTIVE
This study aims to investigate the regulatory role of p38 mitogen-activated protein kinase (p38MAPK) in rats with lower-extremity arterial ischemia-reperfusion injury.
MATERIALS AND METHODS
A total of 60 Sprague-Dawley (SD) rats were randomly divided into four groups: control group (Group A), lower-extremity arterial ischemia-reperfusion group (Group B), lower-extremity arterial ischemic postconditioning group (Group C), and lower-extremity arterial ischemic postconditioning + SB203580 group (Group D, 5 μmol/L SB203580, the inhibitor of MAPK pathway, was injected after lower-extremity arterial ischemic postconditioning). The lower-extremity arterial vessels were collected after 24 h. The apoptosis in the lower-extremity arterial vessel in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The expression of phosphorylated (p)-p38MAPK was measured via Western blotting, and the level of p-activating transcription factor-2 (ATF-2) was detected via immunohistochemical method.
RESULTS
The positive rate of apoptotic cells (%) in Group B was significantly increased compared to that in Group A (p<0.05). However, the positive rate was statistically decreased by postcondition in Group C, the rate was further reduced after injection of SB203580 in Group D compared to Group B (p<0.05). Compared with that in Group C, the expressions of p-p38MAPK and p-ATF-2 in Group D were significantly downregulated after injection of SB203580 (p<0.05).
CONCLUSIONS
Lower-extremity arterial ischemia-reperfusion postconditioning can significantly reduce the apoptosis level in vascular tissues, decrease the expressions of p-p38MAPK and downstream factor ATF-2, and alleviate the damage in lower-extremity arterial vessels. The inhibition of MAPK pathway further restricted the apoptosis and contributed to a promoting role in the recovery of lower-extremity arterial ischemia-reperfusion injury.
目的
本研究旨在探讨丝裂原活化蛋白激酶 p38（p38MAPK）在大鼠下肢动脉缺血再灌注损伤中的调节作用。
材料与方法
60 只 Sprague-Dawley（SD）大鼠随机分为四组：对照组（A 组）、下肢动脉缺血再灌注组（B 组）、下肢动脉缺血后处理组（C 组）和下肢动脉缺血后处理+SB203580 组（D 组，5μmol/L SB203580，MAPK 通路抑制剂，下肢动脉缺血后处理后注射）。24 小时后采集各组下肢动脉血管。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法（TUNEL）检测各组下肢动脉血管细胞凋亡情况。采用 Western blot 法检测磷酸化 p38MAPK（p-p38MAPK）的表达，免疫组化法检测激活转录因子-2（ATF-2）的水平。
结果
与 A 组相比，B 组细胞凋亡阳性率（%）明显升高（p<0.05）；而 C 组经后处理后，阳性率降低，D 组经 SB203580 注射后，与 B 组相比，阳性率进一步降低（p<0.05）。与 C 组相比，D 组注射 SB203580 后，p-p38MAPK 和下游因子 ATF-2 的表达明显下调（p<0.05）。
结论
下肢动脉缺血再灌注后处理可显著降低血管组织细胞凋亡水平，降低 p-p38MAPK 及其下游因子 ATF-2 的表达，减轻下肢动脉损伤；抑制 MAPK 通路进一步限制细胞凋亡，促进下肢动脉缺血再灌注损伤的恢复。
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