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家蝇(Musca domestica)蛆富含蛋白质的提取物通过促进胆汁酸生成及随之而来的胆固醇消耗,减轻了载脂蛋白E缺陷小鼠的动脉粥样硬化。

Protein-enriched extracts from housefly (Musca domestica) maggots alleviates atherosclerosis in apolipoprotein E-deficient mice by promoting bile acid production and consequent cholesterol consumption.

作者信息

Xian Cuiling, Lai Disheng, Liu Jiaming, Li Shixin, Cao Junlin, Chen Kengyu, Liang Dajun, Fu Nanlin, Wang Yan, Xiao Mingzhu

机构信息

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

出版信息

Arch Insect Biochem Physiol. 2022 Oct;111(2):e21951. doi: 10.1002/arch.21951. Epub 2022 Jul 5.

Abstract

Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein-enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti-atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE ) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8-week-old male ApoE mice were recruited and fed on a cholesterol-enriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real-time quantitative polymerase chain reaction and western blot were employed to determine the expression of hepatic ATP-binding cassette transporter A1 (ABCA1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor-γ (PPAR-γ). Serum levels of high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), and total cholesterol (TC) were determined by enzyme-linked immunoassay. Results revealed that PE reversed the formation of atherosclerotic lesion; increased the expression of PPAR-γ, LXRα, and ABCA1; increased the amount of bile flow and total bile acid; reduced the serum level of LDL and TC; and increased the level of HDL. In conclusion, enhancement on bile acid production and consequent cholesterol consumption may partially contribute to the anti-atherosclerotic effects of PE. The reversal of PPARγ-LXRα-ABCA1 signaling pathway may be involved in this process.

摘要

目前,控制动脉粥样硬化对于预防未来的心脏病发作或中风至关重要。家蝇幼虫(家蝇)富含蛋白质的提取物(PE)可通过其抗氧化作用部分抑制动脉粥样硬化的发展。PE是否发挥其他抗动脉粥样硬化功能仍不清楚。在此,发现PE可同时促进载脂蛋白E基因敲除(ApoE)小鼠的胆固醇代谢。胆汁酸合成在调节动脉粥样硬化中的胆固醇稳态中起关键作用。进一步探讨了PE是否通过促进胆汁酸生成及随后的胆固醇消耗来减轻动脉粥样硬化。首先,招募8周龄雄性ApoE小鼠,用富含胆固醇的饮食喂养。8周后,将这些小鼠分为三组,再分别给予PE、辛伐他汀和生理盐水灌胃8周。然后评估动脉粥样硬化的严重程度。采用实时定量聚合酶链反应和蛋白质印迹法测定肝脏ATP结合盒转运蛋白A1(ABCA1)、肝脏X受体α(LXRα)和过氧化物酶体增殖物激活受体-γ(PPAR-γ)的表达。通过酶联免疫测定法测定血清中高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)和总胆固醇(TC)的水平。结果显示,PE可逆转动脉粥样硬化病变的形成;增加PPAR-γ、LXRα和ABCA1的表达;增加胆汁流量和总胆汁酸量;降低血清LDL和TC水平;并提高HDL水平。总之,胆汁酸生成增加及随后的胆固醇消耗增加可能部分有助于PE的抗动脉粥样硬化作用。PPARγ-LXRα-ABCA1信号通路的逆转可能参与了这一过程。

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