大蒜素通过PPARγ/ERRα/PGC-1β通路改善动脉粥样硬化小鼠的骨质量
Allicin improves bone quality in atherosclerotic mice through the PPARγ/ERRα/PGC-1β pathway
  
DOI:10.3969/j.issn.1006-7108.2026.01.001
中文关键词:  动脉粥样硬化  骨质疏松  骨代谢  大蒜素  PPARγ/ERRα/PGC-1β
英文关键词:atherosclerosis  osteoporosis  bone metabolism  allicin  PPARγ/ERRα/PGC-1β
基金项目:国家自然科学基金项目(82261138556);2024年国家中医药管理局中医药国际合作专项(XDZYJZC-002)
作者单位
郭昊辰1 徐天舒1 梁瑞琼1 沈今1 戴铮泽1 李勇奇1 王丽丽2 郭淑贞1 张东伟1* 1.北京中医药大学中医学院北京 102488 2.北京中医药大学中药学院北京 102488 
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中文摘要:
      目的 探究大蒜素对动脉粥样硬化模型小鼠骨代谢的改善作用及其潜在作用机制。方法 SPF级ApoE?/?雄性小鼠经高脂饲料喂养8周后,采用随机分组法进行分组,每组8只,包括模型组、大蒜素组及阿托伐他汀组,连续给药9周。另取C57BL/6N野生型小鼠8只,作为对照组,给予普通饲料常规喂养。利用生化法测定小鼠血脂变化,包括总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平。利用ELISA法测定血清骨吸收标志物,包括TRAP和CTX-1的变化。此外,利用Micro-CT检测小鼠骨微结构改变,并通过傅里叶变换红外光谱法检测骨材料特性,利用HE染色与TRAP染色观察骨组织病理学变化,利用Western blotting检测骨组织内骨吸收以及PPARγ/ERRα/PGC-1β通路相关蛋白的表达。结果 大蒜素干预能显著降低动脉粥样硬化小鼠的血清TG、TC、HDL-C和LDL-C水平,同时抑制小鼠骨微结构的破坏,改善骨材料特性,以及抑制骨组织结构的病理损伤。此外,大蒜素能下调动脉粥样硬化小鼠血清中TRAP与CTX-1的水平,并降低其骨组织NFATc1、c-Fos、Cathepsin K蛋白的表达,抑制PPARγ、ERRα和PGC-1β蛋白的表达。结论 大蒜素能通过抑制PPARγ/ERRα/PGC-1β通路,改善动脉粥样硬化小鼠的骨质量,进而防治骨质疏松的发生和发展。
英文摘要:
      Objective To explore the effect of allicin on bone metabolism in atherosclerotic mice and its potential mechanism of action. Methods After 8 weeks of feeding with a high-fat diet, SPF-grade male ApoE?/? mice were grouped using a random grouping method, with 8 mice in each group, including the model group, the allicin group, and the atorvastatin group. Mice were administered drugs continuously for 9 weeks. In addition, 8 C57BL/6N wild-type mice were taken as the control group and fed with a regular diet routinely. Biochemical methods were used to determine the serum lipid levels in mice, including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). ELISA were used to determine the changes in serum bone resorption markers, including TRAP and CTX-1. Meanwhile, micro-CT was used to scan the bone microstructure of mice. Fourier transform infrared spectroscopy was applied to detect bone material properties. HE staining and TRAP staining were performed to observe the pathological structure of bone tissue. Western blotting was used to detect the expression levels of bone resorption-related proteins (NFATc1, c-Fos, Cathepsin K) and proteins related to the PPARγ/ERRα/PGC-1β pathway in the bone tissue. Results Allicin intervention significantly reduced the serum levels of TG, TC, HDL-C, and LDL-C in atherosclerotic mice, while inhibiting the destruction of bone microstructure, improving bone material properties, and alleviating the pathological damage of bone tissue. In addition, allicin down-regulated the serum levels of TRAP and CTX-1 in atherosclerotic mice, decreased the expressions of NFATc1, c-Fos, and Cathepsin K proteins in the bone tissue, and inhibited the expressions of PPARγ, ERRα, and PGC-1β proteins. Conclusion Allicin improves bone quality in atherosclerotic mice by inhibiting the PPARγ/ERRα/PGC-1β pathway, thereby preventing and treating the occurrence and development of osteoporosis.
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