基于miR-33a-ABCA1/G1途径调节胆固醇逆转运探讨熊氏十味温胆汤抗动脉粥样硬化作用机制
批准号:
81603600
项目类别:
青年科学基金项目
资助金额:
18.0 万元
负责人:
谢雪姣
依托单位:
学科分类:
H3108.中医内科学
结题年份:
2019
批准年份:
2016
项目状态:
已结题
项目参与者:
曾恒、龚勇珍、范崇源、苏联军、邹旭峰、徐佳、刘国华
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中文摘要
血管壁内过量胆固醇蓄积是动脉粥样硬化(As)发生发展的关键环节。胆固醇逆向转运(RCT)是机体清除过多胆固醇唯一途径,为调脂抗As的关键机制。miR-33a通过靶向下调ABCA1/G1抑制RCT。前期研究发现基于“阳微阴弦”之“虚痰瘀”病机的熊氏十味温胆汤(XSWD)有调脂抗As作用,其机制不清。预实验显示XSWD降低THP-1细胞miR-33a水平,上调ABCA1/G1表达。因此,我们提出“XSWD通过调节miR-33a-ABCA1/G1通路促RCT而抗As”的科学假说。拟采用apoE-/-小鼠研究XSWD促RCT抗As作用;在此基础上用THP-1细胞模型,采用基因过表达和沉默技术,研究此方是否通过miR-33a-ABCA1/G1途径促细胞内RCT,从而抗As。预期本研究可从RCT角度为该方的应用提供实验依据,进一步验证和丰富胸痹心痛“阳微阴弦”病机内涵,为中医药防治As提供新思路。
英文摘要
Excessive deposited cholesterol on the vascular wall is the key factor in contribution to the development of arthrosclerosis (As). Reversal cholesterol transportation (RCT) is the single path to cholesterol efflux, which is the critical mechanism in regulation of cholesterol metabolism. Considerable evidence suggests that miR-33a and their target gene ABCA1/ABCG1 may contribute to the RCT. Our Studies have indicated Xiong’s shiwei wendan decoction (XSWD) can regulate the cholesterol metabolism and has an anti-arthrosclerosis function. XSWD is based on “Yang Wei Yin Xian” (Yang Qi Deficiency mixed with Yin fluid accumulated cause tight vessel/wiry pulse) clinical manifestation, corresponded to the pathology of Deficiency, Phlegm and Stasis in the traditional Chinese medical theory. It still remains unclear about the detail mechanism of how the XSWD works to anti-arthrosclerosis. Our previous study suggested that XSWD can downregulate the miR-33a level and upregulate the ABCA1/ABCG1 expression in THP-1 cells. So we hypothesized that XSWD might exert a direct effect on regulating the molecular pathway of miR-33a-ABCA1/G1 to achieve anti-Arthrosclerosis. Based on this hypothesis, in this study we will first survey the effect of XSWD on the triglyceride, cholesterol level, RCT level and evaluate the pathology condition of arthrosclerosis of apoE-/-mice model in vivo. Furthermore, we will investigat the ability of XSWD to activate cholesterol efflux and to affect miR-33a-ABCA1/G1 expression by using gene overexpression and siRNA silence technique on the THP-1 cellular model. This study will aim to investigate the mechanism of XSWD for anti-arthrosclerosis by the way of miR-33a-ABCA1/G1. And our study may further prove or provide more information about “Yang Wei Yin Xian” for Xiong Bi Syndrome (Chest Blockage Syndrome). The study might open a new research direction to better understand molecular mechanisms against arthrosclerosis of herbal and to find more potential product from Chinese herbal .
血管壁内过量胆固醇蓄积是动脉粥样硬化(Atherosclerosis,As)发生发展的关键环节。胆固醇逆向转运(Reverse Cholesterol Transport,RCT)是机体清除过多胆固醇唯一途径,为调脂抗As的关键机制。miR-33通过靶向下调ABCA1抑制RCT。前期研究发现基于“阳微阴弦”之“虚痰瘀”病机的熊氏十味温胆汤(Xiong's shiwei wendan decoction, XSWD)有调脂抗As作用,其机制不清。我们结合运用生物信息学、蛋白质生物化学、细胞生物学等方法与技术,采用apoE-/-小鼠研究XSWD促RCT抗As作用,研究发现XSWD可显著降低能显著改善ApoE-/-小鼠血清血脂水平,且可使ApoE-/-小鼠主动瓣和主动脉官腔内脂质沉积斑块明显削减、减轻肝脏内脂质沉积。以上显示XSWD调节小鼠脂质代谢,缓解动脉粥样硬化进程。在此基础上构建RAW264.7泡沫细胞模型,采用基因过表达miR-33,发现本方可减少泡沫细胞脂质蓄积、促进胆固醇流出,提高ABCA1表达。研究结果显示本方通过miR-33-ABCA1途径促细胞内RCT,从而抗AS。综合上述结果显示,本研究可从RCT角度为该方的应用提供实验依据,进一步验证和丰富胸痹心痛“阳微阴弦”病机内涵,为中医药防治As提供新思路。
期刊论文列表
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DOI:--
发表时间:2019
期刊:中医学报
影响因子:--
作者:曾思宇;谢雪姣;刘国华;马星雨
通讯作者:马星雨
DOI:--
发表时间:--
期刊:中国中医药现代远程教育
影响因子:--
作者:谢雪姣;曾思宇;肖刘成;林丽美;朱浩;范崇源
通讯作者:范崇源
DOI:10.1016/j.cca.2019.12.027
发表时间:2019-12
期刊:Clinica chimica acta; international journal of clinical chemistry
影响因子:--
作者:Rong-Jie Zhang;Yu-Fang Yin;Xue-Jiao Xie;Hong-Feng Gu
通讯作者:Rong-Jie Zhang;Yu-Fang Yin;Xue-Jiao Xie;Hong-Feng Gu
Autophagy: a killer or guardian of vascular smooth muscle cells
自噬:血管平滑肌细胞的杀手或守护者
DOI:10.1080/1061186x.2019.1705312
发表时间:2019-12
期刊:Journal of Drug Targeting
影响因子:4.5
作者:Yin-Yu Zhang;Ya-Ning Shi;Neng Zhu;Wei Wang;Chang-Feng Deng;Xue-Jiao Xie;Duan-Fang Liao;Li Qin
通讯作者:Li Qin
DOI:--
发表时间:2019
期刊:中国临床药理学与治疗学
影响因子:--
作者:聂娟;曹玉梅;杨冬梅;孙四玉;王巧琼;谢雪姣;庹勤慧
通讯作者:庹勤慧
基于线粒体自噬途径探讨血管平滑肌细胞衰老的机制及熊氏十味温胆汤的干预作用
- 批准号:2025JJ90023
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2025
- 负责人:谢雪姣
- 依托单位:
基于激活AMPK/mTOR途径介导的脂噬探讨熊氏十味温胆汤抗动脉粥样硬化作用机制
- 批准号:2021JJ30510
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2021
- 负责人:谢雪姣
- 依托单位:
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