钙化性主动脉瓣狭窄脂质代谢异常的代谢组学研究

The exact mechanism for aortic stenosis is not clealy understood.A number of theories have been proposed but none is entirely satisfactory. The most popularly accepted pathophysiology is that of atherosclerosis, lipid deposition and inflammation. Genetic studies demonstrated that lipid, Vitamin D receptor gene and Notch1 signaling have important implications in the development of CAVS, but no specific gene has yet been identified. By 1H NMR (nuclear magenetic resonance spectroscopy) analysis, our previous work showed that the unsaturated lipid and very low density lipoprotein (VLDL) were abnormal in blood sample. Through metabonomic study on blood sample and valve tissue for calcific aortic stenosis patients, the purpose of our study are (1) to compare the unsaturated lipid and VLDL in valve tissue with A type aortic dissection patients (aortic valve replacement needed). (2) to compare the differences of unsaturated lipod and VLDL between valve tissue and blood sample. (3) to study the relationship between inflammatory factors and lipid metabolism in calcific aortic stenosis patients.

钙化性主动脉瓣狭窄（CAVS）的发生机制尚未完全阐明，其病理生理改变包括动脉粥样硬化、脂质沉积和炎性反应。基因研究表明脂质、维生素D受体和Notch1信号都和CAVS的发生相关，但这些基因也和其他疾病相关。我们前期通过1H核磁共振质谱分析发现CAVS患者血液中的不饱和脂肪酸和极低密度脂蛋白代谢异常。在此基础上，我们通过对主动脉瓣狭窄患者血液和离体瓣膜组织（瓣膜置换术后）的代谢组学分析：（1）比较主动脉瓣狭窄组和A型主动脉夹层对照组（需进行主动脉瓣膜置换者）瓣膜组织的不饱和脂肪酸和极低密度脂蛋白代谢，确定CAVS患者瓣膜组织上是否存在脂质代谢异常；（2）比较主动脉瓣狭窄患者血液和瓣膜组织脂质代谢之间的异同，寻找是否有独立于机体整体或局部改变而存在的单独瓣膜病变；（3）对比主动脉瓣狭窄病例组和正常健康对照组的血脂水平及炎性反应指标，探寻血脂指标和炎性因子与CAVS脂质代谢之间的关系。

钙化性主动脉瓣狭窄（CAVS）的发生机制尚未完全阐明，其病理生理改变包括动脉粥样硬化、脂质沉积和炎性反应。基因研究表明脂质、维生素D 受体和Notch1 信号都和 CAVS 的发生相关，但这些基因也和其他疾病相关。我们通过对主动脉瓣狭窄患者血液和离体瓣膜组织（瓣膜置换术后）的代谢组学分析：（1）主动脉瓣狭窄患者和正常健康对照者血液样本的代谢组学结果显示：病例组卵磷脂（FAC PC）水平失调，与正常对照组相比，FAC PC（18::0，18:2，20:3）水平下调，而FAC PC （16:0/22:6）水平上调。鞘磷脂（18:1/22:0）水平下调。（2）主动脉瓣狭窄组瓣膜组织及A型夹层患者主动脉瓣膜组织（对照组）的代谢组学研究结果显示：正常瓣膜组织细胞间质中焦磷酸盐水平明显高压钙化的瓣膜组织（p=0.0001）。钙化性主动脉瓣狭窄患者存在脂质代谢异常，主要是磷脂代谢异常。