中文摘要
异病同治和同病异治是中医辨证论治体系的重要内容。脏器纤维化(如肝、肺、肾等)是多种慢性疾病的共同病理特征,由此导致的脏器功能衰竭是患者致残、死亡的主要原因。目前脏器纤维化的发病机制仍不十分清楚,尚未找到用于早期诊断的生物标志物,几乎没有专门针对纤维化的治疗药物。而中药具有多成分、多环节、多靶点的作用特点,对病理复杂的疾病可发挥综合优势。前期研究结果显示蒙古扁桃对肝、肺和肾纤维化显示出一定的防治作用。本项目拟通过建立稳定的大鼠肝、肺、肾纤维化模型,结合组织学、纤维化、生理生化等药效学指标筛选蒙古扁桃抗器官纤维化的有效部位及有效剂量,分离鉴定其有效成分,采用分子生物学、代谢组学等方法,从整体、器官、蛋白、分子等多水平探讨蒙古扁桃抗肝、肺、肾纤维化的物质基础及作用机制,以期揭示器官纤维化的实质,为寻找通治多器官纤维化和挖掘抗纤维化的有效药物提供科学依据,为中医异病同治、同病异治理论提供实验依据。
英文摘要
Treating different diseases with same method and treating same disease with different methods have profound theoretical origins as an important content of TCM syndrome differentiation and treatment system. Organ fibrosis (such as liver, lung, kidney, etc.), is a common pathological features of a variety of chronic diseases. Organ failure caused by organ fibrosis is the main reason of disability and death in patients. Chinese medicine has a multi-component, multi-link, multi-target action features. Preliminary results showed that Amygdalus mongolica had a preventive effect on prevention and treatment of liver, lung and kidney fibrosis.In this project, Through the establishment of stable rat liver, kidney, lung fibrosis model, and administered to medicinal decoction and its petroleum ether, ethyl acetate, n-butanol, water parts of different doses, analysis the fibrosis markers, biochemical indicators, determined of indicators histology, antioxidant and molecular biology, screened effective part of Amygdalus mongolica and effective dose for the protective effect of organ fibrosis, and Isolation and identification of the active ingredient. From different levels a whole, organs, cells, proteins, molecules, etc. To explore the mechanism of action and the material basis of Amygdalus Mongolica prevention and treatment of kidney, lung fibrosis.To search for effective drugs for common treatment of multiple organ fibrosis, so as to reveal the essence of fibrosis and sclerosis of organs and open a new way for TCM prevention and treatment of refractory diseases; to provide experimental basis for TCM theory of treating different diseases with same method and treating same disease with different methods.
结题摘要
本项目在一年期应急管理项目的支持下---主要开展蒙古扁桃Amygdalus mongolica(AM)抗肝纤维化Liver Fibrosis(LF)的物质基础和作用机制研究---以CCl4诱导大鼠LF模型,并灌胃给予蒙古扁桃药材水煎液、总提物和系统溶剂法得到石油醚、乙酸乙酯、正丁醇、水部位不同剂量,通过对其纤维化指标、组织形态学、抗氧化系统、血清和组织生理生化指标等测定和分析,筛选AM抗LF有效部位及有效剂量,分离鉴定有效成分;并基于多种现代色谱和波谱技术、代谢组学、分子生物学等方法,探讨AM抗LF的作用机制及物质基础。主要结论:1)AM药材水煎制剂及总提物(生药量为0.5g/kg、1g/kg、2g/kg、4g/kg)对CCl4致大鼠LF具有保护作用,总提物1g/kg、2g/kg显示较好作用;2)蒙古扁桃药材石油醚部位(AM-PE)及其正丁醇部位(AM-NA)为抗LF的有效部位,AM-PE(0.75g/kg、1.25g/kg、1.75g/kg)尤以1.25g/kg剂量、AM-NA(1.25g/kg、1.5g/kg、1.75g/kg)尤以1.5g/kg剂量组作用佳;3)AM-PE的GC/MS表明不饱和脂肪酸占73.20%(油酸占28.87%,亚油酸占38.69%),饱和脂肪酸占19.66%(以棕榈酸为主)。4)对以石油醚为溶剂的提取蒙古扁桃油的最佳工艺、GC-MS、理化性质、重金属含量、安全性评价研究表明,符合国家食用油卫生和安全标准,属于无毒级。5)首次从AM-NA中分离得到苦杏仁苷单体,苦杏仁苷在AM-NA中所占质量比重为47.72%,苦杏仁苷(20mg/kg、40mg/kg、80mg/kg)对CCl4致大鼠LF具有较好保护作用。6)AM-PE、AM-NA及苦杏仁苷具有清除活性氧及抗脂质过氧化作用, 能够拮抗 CCl4 的毒性,抑制细胞外基质的形成;下调TGF-β1/Smads信号传导通路中Smad3 mRNA的表达。7)代谢组学研究中,从LF大鼠尿液中筛选鉴定得到9个与LF发生发展密切相关的关键潜在生物标志物,主要参与色氨酸代谢,酰胺生物合成,三羧酸循环;AM-PE高、中剂量及AM-NA中、低剂量能显著回调LF大鼠尿液代谢轮廓,从而改善LF。其具体通过何生物标志物及通路发挥抗LF机制还在进一步分析中。8)发表论文2篇,SCI收录1篇,核心1篇,培养硕士生2名。
