首页|辣椒素纳米胶囊通过抑制PI3K/Akt/GSK-3β途径改善心肌纤维化的研究

辣椒素纳米胶囊通过抑制PI3K/Akt/GSK-3β途径改善心肌纤维化的研究

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目的 探讨辣椒素纳米颗粒(Capsaicin/Nanoparticles,Cap/NPs)胶囊对大鼠心肌梗死后心肌纤维化及磷酸肌醇3激酶/蛋白激酶B/糖原合成酶激酶3β(Phosphatidylinositol Kinase 3-Kinase/Protein Kinase B/Glycogen Synthase Kinase 3β,PI3K/Akt/GSK-3β)信号通路的影响.方法 于2022年1月—2023年6月自贵州医科大学动物中心购进40只雄性健康Sprague-Dawley(SD)大鼠,在适应性喂养7 d后,按随机数表法分为4组(正常对照组、假手术组、模型组、干预组),每组10只.正常对照组、假手术组、模型组予以生理盐水,干预组予以Cap/NPs胶囊口服,1次/周,连续4周.对模型组与干预组行手术结扎,构建心肌梗死模型,假手术组则开展相同手术操作不予以结扎处理,对照组为正常大鼠.术后4周,观察各组心肌纤维化情况,检测PI3K/Akt/GSK-3β通路蛋白在大鼠心肌组织中表达情况.结果 模型组血清激活素A(Activin A,ACT-A)水平为(2.33±0.28)pg/mg、心房钠尿肽(Atrial Natriuretic Peptide,ANP)水平为(2.21±0.57)pg/mg、脑钠肽(Brain Natriuretic Peptide,BNP)水平为(212.04±17.36)ng/L、基质金属蛋白酶-9(Matrix Metalloproteinases,MMP-9)水平为(221.65±23.34)ng/L、胶原纤维蛋白Ⅲ水平为(67.62±1.85)ng/mL,各指标均明显高于干预组,差异有统计学意义(P均<0.05).模型组大鼠心肌组织PI3K/Akt/GSK-3β蛋白表达水平明显低于干预组,差异有统计学意义(P<0.05).结论 大鼠心肌梗死模型建立后予以Cap/NPs胶囊干预,能够有效抑制心肌纤维化发展,减轻大鼠心肌损伤,其机制与PI3K、Akt、GSK-3β蛋白活性调控以及PI3K/Akt/GSK-3β信号通路传导抑制有关.
Study of Capsaicin Nanoparticles Capsules Ameliorating Myocardial Fi-brosis by Inhibiting the PI3K/Akt/GSK-3β Pathway
Objective To investigate the effects of capsaicin/nanoparticles(Cap/NPs)capsules on myocardial fibrosis and phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3β(PI3K/Akt/GSK-3β)signaling path-way after myocardial infarction in rats.Methods From January 2022 to June 2023,40 healthy male Sprague Dawley(SD)rats were purchased from the Animal Center of Guizhou Medical University.After adaptive feeding for 7 days,they were randomly divided into 4 groups(normal control group,sham operation group,model group,intervention group)using a random number table method,with 10 rats in each group.The normal control group,sham operation group,and model group were given physiological saline,while the intervention group was given Cap/NPs capsules orally once a week for 4 consecutive weeks.The model group and intervention group were surgically ligated to prepare myocardial infarction models,while the sham operation group underwent the same surgical operation without ligation,and the control group was normal rats.Myocardial fibrosis was observed 4 weeks after surgery,and the expression of PI3K/Akt/GSK-3β pathway proteins in rat myocardial tissue of difference groups were detected.Results Serum ac-tivin A(ACT-A)(2.33±0.28)pg/mg,atrial natriuretic peptide(ANP)(2.21±0.57)pg/mg,brain natriuretic peptide(BNP)(212.04±17.36)ng/L,matrix metalloproteinase-9(MMP-9)(221.65±23.34)ng/L,and collagen fibrillin Ⅲ(67.62±1.85)ng/mL indicators were significantly higher than those in the intervention group,and the differences were statistically significant(all P<0.05).The expression level of PI3K/Akt/GSK-3β protein in myocardial tissues of rats in the model group was significantly lower than that in the intervention group,and the difference was statistically signifi-cant(P<0.05).Conclusion Cap/NPs capsule intervention after the establishment of rat myocardial infarction model can effectively inhibit the development of myocardial fibrosis and reduce myocardial injury in rats,and its mechanism is the regulation of PI3K,Akt,GSK-3β protein activity,which is related to the inhibition of PI3K/Akt/GSK-3β signal-ing pathway.

PI3K/Akt/GSK-3β signaling pathwayMyocardial infarctionMyocardial fibrosisCapsaicin/nanoparticles capule

梅毅、杨吉

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浙江省人民医院毕节医院心胸血管外科,贵州毕节 551705

PI3K/Akt/GSK-3β信号通路 心肌梗死 心肌纤维化 辣椒素纳米颗粒胶囊

毕节市科学技术联合基金

毕科联合字SY[2019]12号

2024

系统医学

系统医学

ISSN:
年,卷(期):2024.9(3)
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