ERK介导的炎性反应参与肾缺血再灌注损伤

目的研究小鼠肾缺血再灌注损伤的发病机制。方法建立小鼠肾缺血再灌注损伤模型。12只雄性C57BL／6随机分为2个组（n=6），分别为假手术组（Sham），肾缺血再灌注损伤模型组（IRI）。IRI组血管夹夹闭左肾动脉，置于32℃温箱后1h松开血管夹，去除右肾。Sham组操作同上，但不夹闭左肾动脉。再灌注24h后处死小鼠，收集血清和肾脏标本。测定血清肌酐（Cr）和血尿素氮（BUN）。PAS染色后显微镜下观察肾脏形态学变化，Western印迹分析ERK、p-ERK的表达，PCR检测MCP-1、IFN-γ。结果与假手术组（Sham）相比，IRI组血清肌酐、血尿素氮明显升高，病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显，还可观察到炎性细胞浸润明显增加。ERK、p-ERKWestern印迹结果PCR显示MCP-1、TNF-α也明显上调，但ERK表达不变。结论在肾缺血再灌注中，ERK激活介导的炎性后府可能参与了肾扣伤。

ERK-Mediated Inflammation Is Involved in Renal Ischemia/Reperfu- sion Injury

Objective To explore the mechanism of renal ischemia/reperfusion （I/R） injury in mice. Methods The renal I/R injury- models were established in mice. Twelve male C57BL/6 mice were randomly divided into two groups： sham group and I/R injury （IRI） group. The mice in the IRI group underwent clamping of the renal pedieles, then remained in the 32℃ incubator for 1 hour, and had their right kidneys removed. The mice in the sham group received the same proce- dures except clamping of the renal pedicles. These animals were sacrificed after 24 h of reperfu- sion. The blood samples were collected and measured for the levels of serum creatinine （Cr） and u- rea nitrogen （BUN） . The pathological changes of renal tissues were observed after PAS stai- ning. The mRNA levels of MCP-1 and TNF-α were measured by Q-PCR. The expression of extracel- lular signal-regulated kinase （ERK） and p-ERK was measured by Western blotting. Results The levels of Cr and BUN were significantly increased in the IRI group compared with the sham group. Pathological examination revealed a great number of swollen necrotic renal tubular epithelial cells, the formation of protein casts and increased inflammatory infiltrates in the IRI group. Moreover, the mRNA levels of MCP-land TNF-α, and the expression of p-ERK were signifi- cantly up-regulated in the IRI group. But there was no significant difference in the expression of ERK between the two groups. Conclusions The ERK-mediated inflammation is involved in the renal I/Rinjury.