探讨新活素对急性心肌梗死大鼠心脏重构、血管生成及NF2/Mst1信号通路的影响。方法 50只雄性大鼠按随机数字法分为假手术组、模型组、低剂量rhBNP组、中剂量rhBNP组、高剂量rhBNP组，均10只。除假手术组外，建立急性心肌梗死动物模型，建模成功后，低、中及高剂量rhBNP组大鼠颈静脉输注5、10及15μg/kg的rhBNP溶液，其余大鼠颈静脉输注等体积生理盐水。心脏超声检测LVIDd、LVIDs、LVEDV、LVESV；BL-420生物机能实验检测LVEDP、±dp/dt max；测量BW、THW/BW、LVW/BW；TUNEL法检测心肌细胞凋亡率；免疫组化检测心肌组织血管生成；免疫印迹检测心肌组织NF2、Mst1、Bax及Bcl-2蛋白表达。 结果 与假手术组相比，模型组大鼠LVIDd、LVIDs、LVEDV、LVESV、LVEDP、THW/BW、LVW/BW、心肌细胞凋亡率、NF2、Mst1、Bax表达均升高（P<0.05），±dp/dt max、Bcl-2表达降低（P<0.05）；与模型组相比，低、中及高剂量rhBNP组LVIDd、LVIDs、LVEDV、LVESV、LVEDP、THW/BW、LVW/BW、心肌细胞凋亡率、NF2、Mst1、Bax表达降低（P<0.05），±dp/dt max、Bcl-2表达升高（P<0.05）。 结论 新活素可显著改善急性心梗大鼠心脏重构，减少心肌细胞凋亡，加快心肌组织血管新生，这与抑制NF2/Mst1信号通路活性相关。
Abstract
Objective To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on cardiac remodeling, angiogenesis, and the NF2/Mst1 signaling pathway in rats with acute myocardial infarction. Methods According to random number method, 50 male rats were divided into sham operation group, model group, the low, medium and high dose rhBNP groups (10 rats separately). Acute myocardial infarction models were established in the remaining rats except the sham group. After successful modeling, the rats in the low, medium and high dose rhBNP groups were injected with 5, 10 or 15μg/kg rhBNP solution in the jugular vein, and the other rats were injected with equal volume of normal saline. LVIDd, LVIDs, LVEDV, LVESV were detected by cardiac ultrasound. LVEDP and ±dp/dt max were detected by BL-420 biological function test. BW, THW/BW, LVW/BW were tested. TUNEL was used to detect the apoptosis rate of myocardial cells. Myocardial angiogenesis was detected by immunohistochemistry. The protein expressions of NF2, Mst1, Bax and Bcl-2 were detected by Western blot. Results Compared with the sham group, rats in the model group showed increased LVIDd, LVIDs, LVEDV, LVESV, LVEDP, THW/BW, LVW/BW, myocardial cell apoptosis rate, and increased expression of NF2, Mst1, Bax (P<0.05), while ±dp/dt max and Bcl-2 expression decreased (P<0.05). Compared with the model group, rats in the low, medium, and high-dose rhBNP groups showed decreased LVIDd, LVIDs, LVEDV, LVESV, LVEDP, THW/BW, LVW/BW, cell apoptosis rate, and decreased expression of NF2, Mst1, Bax (P<0.05), while ±dp/dt max and Bcl-2 expression increased (P<0.05). Conclusions rhBNP can significantly improve cardiac remodeling in rats with acute myocardial infarction, reduce myocardial cell apoptosis, and promote angiogenesis in myocardial tissue, which may be related to the activity inhibition of NF2/Mst1 signaling pathway.
关键词
急性心肌梗死； /
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冻干重组人脑利钠肽； /
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心脏重构； /
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血管生成； /
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神经细丝蛋白； /
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哺乳动物不育系20样激酶1
Key words
Acute myocardial infarction; /
Recombinant human brain natriuretic peptide; /
Cardiac remodeling; /
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Angiogenesis; /
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Neural filament protein; /
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Mammalian sterile 20-like kinase 1
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基金
河北省卫健委医学科学基金（20181254）
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