鹰嘴豆芽素A预防给药抑制心肌缺血再灌注损伤大鼠心肌炎症产生
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陕西省自然科学基础研究计划面上项目(2018JM7087)


Biochanin A prevents myocardial inflammation in rats with myocardial ischemia reperfusion injury
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    摘要:

    【摘要】目的 构建心肌缺血再灌注(MIRI)损伤动物模型,观察鹰嘴豆芽素A预防给药对心肌炎性因子调节酶过氧化物酶体增殖物激活受体ɑ(PPARɑ)、细胞色素P4501A1(Cyp4501A1)、磷脂酰肌醇3激酶(PI3K)和丝氨酸/苏氨酸激酶(AKT)蛋白及mRNA表达的影响。方法 60只SD大鼠适应性喂养2周后按照随机数字法分为假手术组、模型组、雷米普利干预组、鹰嘴豆芽素A低、中和高剂量组,每组10只。灌胃给药2周后,所有大鼠均采用可逆左冠状动脉前降支结扎法构建MIRI模型,假手术组只穿线不结扎,手术后立即收集血液检测心肌酶谱和血清炎性因子含量,收集心脏检测心肌病理学、心肌炎性指标、心肌炎性因子调节酶PPARɑ、Cyp4501A1、PI3K和AKT蛋白及mRNA的表达。结果 心肌组织病理学可见,假手术组心肌纤维排列整齐,模型组有纤维断裂和组织坏死,与模型组相比,各治疗组均明显好转;与假手术组相比,模型组心肌酶CKMB和LDH、心肌和血清炎性因子HsCRP、IL1α、IL6、IL8和TNFα均明显升高(P<0.05),各治疗组相较于模型组明显降低(P<0.05);与假手术组相比,模型组心肌PPARɑ、Cyp4501A1、PI3K和AKT蛋白及mRNA表达水平均明显降低(P<0.05),而各治疗组相较于与模型组则明显升高(P<005)。结论 鹰嘴豆芽素A预防给药对心肌缺血再灌注损伤大鼠心肌炎症因子具有明显抑制作用,其作用机理可能与鹰嘴豆芽素A可调节PPARɑ、Cyp4501A1、PI3K和AKT蛋白及mRNA表达有关。

    Abstract:

    【Abstract】Objective To establish a rat model of myocardial ischemia reperfusion injury (MIRI) and observe the protein and mRNA expression characteristics of inflammatory factors including peroxisome proliferator activated receptor ɑ (PPARɑ), cytochrome P4501A1 (Cyp4501A1), phosphatidylinositol 3kinase (PI3K) and receptor serine/threonine kinases (AKT) in the myocardium after biochanin A administration. Methods After adaptive feeding for two weeks, 60 SD rats were randomly divided into the sham operation group, model group, ramipril group, Biochanin A low, medium, and high dose group. Two weeks after gavage, all rats were used to construct Miri model by reversible ligation of anterior descending branch of left coronary artery. In the sham operation group, only thread was threaded without ligation. Immediately after operation, blood was collected to detect the myocardial enzyme spectrum and serum inflammatory factor content, and the expression characteristics of myocardial pathology, myocardial inflammatory index, PPAR, cyp4501a1, PI3K, Akt protein and mRNA were collected to detect. Results Myocardial histopathology showed that in the sham operation group, myocardial fibers were arranged in order, and there were fiber rupture and tissue necrosis in the model group. Compared with the model group, the myocardial enzymes CK MB and LDH, myocardial and serum inflammatory factors hs CRP, IL1 α, IL6, IL8 and TNFα in the model group were significantly higher (P<005), and the treatment groups were significantly higher (P<005). Compared with the model group, PPAR, cyp4501a1, PI3K, Akt protein and mRNA expression levels in the model group were significantly lower (P<005), while those in each treatment group were significantly higher (P<005). Conclusion Biochanin A has a significant inhibitory effect on the myocardial inflammatory factors in rats with MIRI, and the mechanism may be related to that it can regulate the proteins and RNA expression of PPARa, Cyp4501A1, PI3K, and AKT.

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  • 在线发布日期: 2020-07-10
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