Selective cyclooxygenase-2 inhibitor NS-398 attenuates myocardial fibrosis in mice after myocardial infarction via Snail signaling pathway

Y.-C. Chi, C.-L. Shi, M. Zhou, Y. Liu, G. Zhang, S.-A. Hou

Intensive Care Unit, People’s Hospital of Rizhao, Rizhao, China. aoliehanyoush@163.com

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• Pharmacology

OBJECTIVE: The role of NS-398 in Snail pathway of myocardial cells in mice after myocardial infarction and its effect on myocardial fibrosis were investigated in this study.

MATERIALS AND METHODS: C57BL/6 mice were selected to establish mouse models of myocardial infarction with permanent ligation of anterior descending branch and sham-operation models without ligation. After successful establishment of models, 30 mice were randomly divided into sham-operation group, myocardial infarction group and drug intervention group. The drug intervention group was treated with intraperitoneal injection of NS-398 (5 mg/kg) at 1 week after modeling for 3 weeks. The survival status of mice after operation was monitored, the cardiac function was detected via echocardiography, the collagen levels in heart tissue pathological sections were detected via Masson staining and Sirius red staining. Moreover, the expressions of Snail and type I collagen levels were detected via immunohistochemistry, and the Snail protein expression level and the activity and expression level of E-cadherin protein were detected via Western blotting.

RESULTS: At 4 weeks after establishment of myocardial infarction model, the fibrosis reaction was obvious, and the cardiac function was decreased, accompanied with Snail activation. The administration of NS-398 for 3 weeks inhibited the Snail activity expression and significantly improved the fibrosis degree after infarction. However, it did not improve the cardiac function. Inhibiting Snail improved the fibrosis reaction after infarction, in which Snail/E-cadherin signaling pathway was involved.

CONCLUSIONS: NS-398 improves the myocardial fibrosis in mice after myocardial infarction through inhibiting the Snail signaling pathway.

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