BML-111 inhibits the inflammatory response and apoptosis of renal tissue in rats with hemorrhagic shock by inhibiting the MAPK pathway

S.-Y. Chang, R.-Q. Sun, M. Feng, Y.-X. Li, H.-L. Wang, Y.-M. Xu

Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. xuyuming@zzu.edu.cn

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• Nephrology

OBJECTIVE: The effect of lipoxin receptor agonist BML-111 on acute kidney injury and AKI in rats with hemorrhagic shock (HS) and its mechanism were investigated.

MATERIALS AND METHODS: A model of hemorrhagic shock in Sprague-Dawley (SD) rats was established, and recovered after 30 min of shock. 1 mg/kg BML-111 was intraperitoneally injected at the beginning of resuscitation in group BML-111. The concentration of serum creatinine, serum KIM-1 content, NGAL and inflammatory factors were detected. Renal tissue injury was examined by HE staining; TUNEL staining was used to detect the apoptosis of rat kidney cells. Western blot was performed for the detection of the expression level of MAPK (mitogen-activated protein kinase), Bax, cytochrome C and caspase-3,9 in rat renal tissue.

RESULTS: HE staining showed pathological changes in groups group comparing to sham group. BML-111 group had a significant decrease in renal tissue injury. The scores of renal injury in each group were in accordance with the histological changes. The expression level of inflammatory factors in HS group was significantly higher than that in sham group (p<0.05). After BML-111 intervention, the levels of inflammatory factors in renal tissue were significantly lower than those in HS group (p<0.05). Meanwhile, NGAL and KIM-1 also showed the same trend. TUNEL staining showed that compared with sham group, the number of apoptotic cells in renal tissue of HS group increased significantly, and the apoptosis rate of renal tissue cells in group BML-111 decreased significantly. Western blot showed that the expression level of JNK, p38MAPK, and apoptosis-related protein in HS group was significantly increased, whereas the expression level of p38MAPK and JNK in group BML-111 was significantly decreased.

CONCLUSIONS: BML-111 can reduce the inflammatory response and apoptosis of renal tissue by inhibiting the activation of MAPK signaling pathway in acute renal injury induced by hemorrhagic shock.

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