Intensive Care Unit, People's Hospital of Rizhao, Rizhao, China.
Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5805-5812. doi: 10.26355/eurrev_201712_14028.
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.
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.
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.
NS-398 improves the myocardial fibrosis in mice after myocardial infarction through inhibiting the Snail signaling pathway.
本研究旨在探讨 NS-398 在心肌梗死后心肌细胞蜗牛途径中的作用及其对心肌纤维化的影响。
选择 C57BL/6 小鼠建立永久性前降支结扎的心肌梗死模型和假手术模型。模型成功建立后，将 30 只小鼠随机分为假手术组、心肌梗死组和药物干预组。药物干预组于建模后 1 周开始腹腔注射 NS-398（5mg/kg），连续 3 周。监测术后小鼠的生存状态，通过超声心动图检测心功能，Masson 染色和天狼猩红染色检测心脏组织病理切片中的胶原水平。此外，通过免疫组化检测 Snail 和 I 型胶原的表达水平，通过 Western blot 检测 Snail 蛋白表达水平和 E-钙黏蛋白蛋白的活性和表达水平。
心肌梗死模型建立 4 周后，纤维化反应明显，心功能下降，同时伴有 Snail 激活。连续 3 周给予 NS-398 可抑制 Snail 活性表达，明显改善梗死区纤维化程度，但不能改善心功能。抑制 Snail 可改善梗死区纤维化反应，其中涉及 Snail/E-钙黏蛋白信号通路。
NS-398 通过抑制 Snail 信号通路改善心肌梗死后小鼠的心肌纤维化。
