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通过灵芝PSP抑制Lp-PLA2和H2O2来减少动脉粥样硬化中滋养血管的血管生成:2型糖尿病体内研究

Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2.

作者信息

Wihastuti Titin Andri, Amiruddin Reyhan, Cesa Fibe Yulinda, Alkaf Amalia Istiqamah, Setiawan Meddy, Heriansyah Teuku

机构信息

Brawijaya University, Department of Biomedical Nursing, Faculty of Medicine, Malang, Indonesia.

Master Program of Biomedical, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

出版信息

J Basic Clin Physiol Pharmacol. 2020 Feb 7;30(6):/j/jbcpp.2019.30.issue-6/jbcpp-2019-0349/jbcpp-2019-0349.xml. doi: 10.1515/jbcpp-2019-0349.

DOI:10.1515/jbcpp-2019-0349
PMID:32031980
Abstract

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

摘要

背景 2 型糖尿病(T2DM)是动脉粥样硬化的主要危险因素。T2DM 中的高血糖会导致晚期糖基化终产物(AGE)的形成,进而引发氧化应激和慢性炎症。氧化应激是由于活性氧(ROS)如 H2O2 水平升高而发生的。另一方面,脂蛋白相关磷脂酶(Lp-PLA2)具有促炎作用,会导致动脉粥样硬化斑块不稳定。这种情况会使缺氧细胞刺激缺氧诱导因子α(HIFα)诱导的血管滋养管血管生成。本研究旨在通过降低 H2O2 和 Lp-PLA2 的水平,从而减少糖尿病大鼠模型中血管滋养管血管生成,来了解多糖肽(PSP)作为抗血管生成剂的潜力。此外,本研究还测量了糖尿病大鼠模型的血脂谱与血管滋养管血管生成的关系。方法 采用真实验室实验,对 25 只 Wistar 大鼠(褐家鼠)进行随机后测对照组设计,分为五组;一组正常组和四组高脂饮食(HFD)并皮下注射低剂量链脲佐菌素(30 mg/kg 体重),分别用安慰剂和三种不同剂量的 PSP(50、150、300 mg/kg 体重)进行治疗。结果 方差分析测试(p < 0.05)表明,多糖肽(PSP)喂养对血管滋养管血管生成量的减少(p = 0.00)、血脂谱(总胆固醇和甘油三酯;p = 0.01,p = 0.001)以及 H2O2 量(p = 0.003)有显著影响。Lp-PLA2 的量下降至(p = 0.184)。这一结果表明 PSP 可预防动脉粥样硬化中的炎症。结论 灵芝的 PSP 是 T2DM 中的一种抗血管生成剂。

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