阻断p38MAPK信号通路对大鼠肾脏缺血再灌注损伤的影响

【目的】探讨阻断p38丝裂原活化蛋白激酶（p38MAPK）信号通路对大鼠急性肾缺血再灌注损伤（IRI）的影响。【方法】sD大鼠24只，随机分为3组，每组8只。对照组（S组）：仅结扎右侧肾蒂，左肾蒂游离；缺血再灌注组（IR组）：结扎右侧肾蒂，夹闭左侧肾蒂60min后，开放灌注24h；p38MAPK抑制剂组（SB组）：静脉注射p38MAPK特异抑制剂SB203580（10mg／kg），余同IR组。检测三组血清尿素氮（BUN）、肌酐（Cr）、肿瘤坏死因子（TNF）-α、白介素（IL）-I水平和p38MAPK蛋白表达、组织病理评分并比较。【结果】与S组比较，IR组血BUN、Cr、TNF—α、IL-1水平、p38MAPK蛋白表达量及组织病理评分均显著增加（P〈0．05）；上述指标SB组较IR组显著下降（P〈0．05）。【结论】SB203580能阻断p38MAPK信号通路，减少p38MAPK表达，抑制炎症细胞因子的释放，减轻肾缺血再灌注损伤。

Effect of the Inhibition of p38MAPK Signaling Pathway on Renal Isehemia Reperfusion Injury in Rats

Objective]To explore the effect of the blockade of p38 mitogen-activated protein kinase （p38MAPK） signaling pathway on renal ischemia reperfusion injury（IRI） in rats. Methods] A total of 24 SD rats were randomly divided into 3 groups with 8 rats per group. The control group（group S） only received the ligation of right renal pediele and the liberation of left renal pedicle. The isehemic reperfusion group（group IR） received the ligation of right renal pedicle and reperfusion for 24h after clamping left renal pedicle for 60min. P38MAPK inhibitor group（group SB） received intravenous infusion of p38MAPK inhibitor SB203580 10mg/kg and ischemic reperfusion. Serum urea nitrogen（BUN）, creatinine（Cr）, tumor necrosis factor-alpha（TNF-α）, interleukin-1（IL-1） and p38MAPK protein of 3 groups were detected. Histopathological score was assessed and compared. Results]Compared with group S, serum BUN, Cr, TNF-α, IL-1, p38MAPK protein and histopathological score in group IR were increased markedly（ P %0.05）. Compared with group IR, all above indexes in group SB were decreased markedly（ P〈0.05）. Conclusion] SB203580 can block p38MAPK signaling pathway, reduce the expression of p38MAPK protein, inhibit the release of inflammatory cytokines and attenuates renal IRI.