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蜂王浆对高胆固醇饮食致兔动脉粥样硬化和阿尔茨海默病的影响及其机制
中文摘要

 当今受遗传-社会心理-环境因素的影响,高血压、动脉粥样硬化、老年痴呆等心脑血管疾病的发病率居高不下,严重影响人民的生活质量和生命健康。高胆固醇血症是高血压、动脉粥样硬化、阿尔茨海默病的危险因素,其发生均与遗传和环境因素有关。除遗传外,环境因素对疾病的发病机理有着显著的影响,其中饮食是最主要的环境因素。使用天然的功能性食品作为替代治疗已成为一种新的防治策略。蜂王浆是由工蜂发达的下咽头部腺和上颚腺共同分泌的一种粘稠的浆状物质,是一种使用历史十分悠久的天然功能性食品,具有广泛的药理活性和保健功能,因其良好的抗衰老、降脂、降血压的效果而受到广泛的关注,但对心脑血管疾病的影响尚缺乏系统性的研究。本研究基于前期基础,利用动脉粥样硬化模型、离体血管环灌流模型和阿尔茨海默病模型,系统性研究了蜂王浆对动脉粥样硬化和阿尔茨海默病的影响及其机制,主要研究结果如下: 1、蜂王浆对高胆固醇饮食诱发去卵巢兔动脉粥样硬化模型的影响 通过建立2%高胆固醇饮食诱导去卵巢兔动脉粥样硬化(AS)模型,发现蜂王浆对绝经期兔具有抗AS作用,主要表现为降低血脂,抑制炎症和氧化应激反应,提高NO水平,保护血管内皮功能,降低血压并纠正ANS平衡紊乱,同时通过影响AS血管α-SMA和CD68表达,抑制并稳定AS斑块,有效缓解AS的病理改变。 2、蜂王浆对离体兔胸主动脉环的扩血管作用及机制 利用离体兔胸主动脉环的灌流模型,发现了0.01~10㎎/mL蜂王浆具有明显的扩血管作用,且RJ中含有毒蕈碱受体激动剂,可能是乙酰胆碱样物质,并通过影响NO/cGMP途径和钙通道诱导血管舒张。 3、蜂王浆对兔阿尔茨海默病模型的影响及其机制 采用2%高胆固醇饮食添加微量铜饮水诱发兔阿尔茨海默病(AD)模型,发现蜂王浆能够降低胆固醇水平,调节脑内ApoE和CYP46基因表达,改善BBB通透性,下调BACE1和RAGE的表达,增加LRP1和IDE的表达水平,促进Aβ的降解和清除,最终减少Aβ有关。此外,RJ通过抗氧化作用和增强神经元代谢活性,防止神经元丢失,减轻AD兔脑的病理改变,从而发挥延缓AD发生发展的作用。 综上所述,本研究利用兔动脉粥样硬化模型、离体血管环灌流模型和阿尔茨海默病模型,系统性研究了蜂王浆对动脉粥样硬化和阿尔茨海默病的保护作用及其机制,为蜂王浆在替代或辅助治疗心脑血管疾病的临床应用提供实验依据。 关键词:蜂王浆,动脉粥样硬化,阿尔茨海默病,高胆固醇血症

英文摘要

 Nowadays, due to the influence of genetic-social psychological-environmental factors, the incidence of cardiovascular and cerebrovascular diseases such as hypertension, atherosclerosis, and senile dementia remains high, seriously affecting people's quality of life and health. Hypercholesterolemia is a common risk factor for hypertension, atherosclerosis, and Alzheimer's disease. Most of these diseases are related to genetic and environmental factors. In addition to genetic factors, environmental factors have a significant impact on the pathogenesis of the diseases, of which the diet is the most important environmental factor. The use of natural functional food as an alternative treatment has become a new control strategy. Royal Jelly (RJ), a viscous, pulpy substance secreted by the worker bees developed from hypopharyngeal glands and epithelial glands, is a natural functional health food with a long history of use. It has a various pharmacological activities and health care functions. The anti-aging, hypolipidemic, and hypotensive effects of royal jelly has been well documented, however, the effects of royal jelly on cardiovascular and cerebrovascular diseases has not been systematically studied. Based on our previous studies, this study using atherosclerosis model, isolated rabbit aortic rings perfusion model and Alzheimer's disease model to systematically investigate the effects of royal jelly on atherosclerosis and Alzheimer's disease, the main findings are summarized as follows: 1.Effect of royal jelly on atherosclerotic model in ovariectomized rabbits induced by high cholesterol diet Through the establishment of atherosclerosis (AS) model in ovariectomized rabbits induced by a 2% high cholesterol diet, it was found that royal jelly has anti-AS effect on menopausal rabbits, mainly by lowering blood lipids, inhibiting inflammation, and reducing oxidation stress levels, increasing NO levels, thereby protecting the vascular endothelium function and lowering blood pressure, and correctiong ANS balance disorders, while inhibiting and stabilizing AS plaques by affecting the expression of vascular α-SMA and CD68, and effectively alleviate the pathological changes of AS. 2.Role of royal jelly in vasodilation of isolated rabbit thoracic aortic rings and its mechanism Using a rabbit thoracic aortic rings perfusion model, it was found that 0.01 to 10 ㎎/mL royal jelly has a significant vasodilator effect. RJ contains muscarinic receptor agonist, possibly an acetylcholine-like substance, and induces vasodilation through NO/cGMP pathway and calcium channels. 3.Effect and mechanism of royal jelly on Alzheimer's disease model rabbits The model of Alzheimer's disease (AD) was induced by adding 2% cholesterol diet with trace amounts of copper drinking water. It was found that royal jelly can lower cholesterol levels, regulate the genes expression of ApoE and CYP 46 in brain, improve BBB permeability, and down-regulate BACE1 and RAGE expression, increase the expression levels of LRP1 and IDE, promote the degradation and clearance of Aβ, and finally reduce Aβ. In addition, RJ exerts anti-AD effects through anti-oxidation and enhancement of neuronal metabolic activity, preventing neuronal loss and reducing the pathological changes in AD rabbit brains. Taken together, this study used rabbit atherosclerosis model, isolated rabbit thoracic aortic rings perfusion model and Alzheimer's disease models to systematically explore the protective effects/mechanisms of royal jelly on atherosclerosis and Alzheimer's disease. These data suggest that royal jelly may be useful as an alternative/additive therapeutic strategy against cardiovascular and cerebrovascular diseases. Key words: Royal jelly, Atherosclerosis, Alzheimer's disease, Hypercholesterolemia

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