关键词: 急性肾损伤, microRNA-21, 缺血再灌注损伤, 缺血预处理, p38MAPK

Abstract: ObjectiveTo study the functioning mechanism of microRNA-21（miR-21） and p38MAPK signaling pathway in renal injury of ischemia reperfusion(IR).MethodsMale C57BL/6J mice were divided into four groups based on whether IR was performed: blank control group, IR group, sham operation group and ischemia preconditioning+ischemia reperfusion group (IPC+IR group).Then they were each divided to 8 subgroups according to different time points after IR（0min，5min, 30min, 45min, 2h, 12h, 24h, 48h）. Analyze the renal tissue, miR-21 level, expression level of p38MAPK and p-p38MAPK protein, and pathological injury of kidney.Results(1)Pathology of kidney：there was no obvious renal injury in the blank control group;pathology injury of kidney gradually appeared after IR in IR group and sham-operation group, which peaked at 24h and gradually recovered; after ischemic preconditioning, the tendency of pathological injury of kidney in IPC+IR group was parallel to that in IR group, but the injury of each subgroup was milder than IR group, and there was statistical difference in the score of renal tubular pathological injury between IPC+IR group and IR and sham-operation group（P<0.01）. (2)p38MAPK expression level: there was no statistical difference in the relative expression level(p-p38MAPK/β-actin） among the groups at the 8 time points(P>0.05). (3)The relative expression level of p-p38MAPK(p-p38MAPK/p38MAPK):there was no obvious expression in blank control group; in IR group, the relative expression level of p-p38MAPK increased rapidly at 15min after IR and peaked at 2h, and remained at a relatively high level afterwards.After ischemic preconditioning, the tendency of the relative expression level of p-p38MAPK in IPC+IR group was parallel to that in IR group,and the level peaked at 2h, but it was lower in each of the 8 subgroups than in the IR group and sham-operation group, the difference being statistical（P<0.01）.（4）Expression level of miR-21:in IR group, with time passing, miR-21 expression increased at 5min after IR and peaked at 24h,being 15.2 times that of baseline, and remained at a relatively high level, while there was no obvious change in miR-21 expression level in blank control group. After ischemic preconditioning,in IPC+IR group, the  expression level of miR-21 remained at the peak level of the IR group at each time points within 48h, which was about 14.8 times that of that of the baseline level,and there was statistical difference between IPC+IR group and sham-operation and IR group（P<0.01）.ConclusionThe possible mechanism of ischemic preconditioning in protecting kidney may be to upregulate miR-21 and inhibit the phosphorylation of p38MAPK in order to reduce the expression of the related downstream inflammatory mediators of p38MAPK signaling pathway.

Key words:

Acute kidney injury, miRNA-21, Ischemia reperfusion injury, Ischemia preconditioning, p38MAPK