蒙药古日古木单、复方对肝损伤的保护作用及JNK通路机制研究

Mongolian medicinal material Gurigumu, named Carthmus tinctorins in Chinese medicine, is mainly used for activating blood circulation and regulating menstruation in Chinese medicine, however, Gurigumu-based compound recipe in Mongolian medicine, such as Gurigumu-13 drugs, is commonly used in Mongolian medicine clinical treatment on liver diseases. Based on good value of Gurigumu compound prescription in Mongolian clinical liver diseases, which is different from traditional Chinese medicine， this project proceeds from the indications. And liver pathological morphological, biochemical functions of the liver, liver cell apoptosis, important cell regeneration factor influence in experimental liver injury models are studied both in vitro and in vivo researches, to make sure whether both single medicinal material of Gurigumu and compound Gurigumu prescription have liver protection and which protection is better on different types of liver injury indeed. Meanwhile this project focuses on the mechanism of JNK signaling pathway, which is widely involved in the regulation of apoptosis, proliferation, metabolism, exercise, DNA damage repair and other life processes, whose functional disorders are closely related to occurrence and development of chronic hepatitis B and other diseases and pathological damages. An important target of this drug treatment may be found in this research on the mechanism of the JNK signaling pathway, which also provides the basis on more powerful molecular level.

古日古木，即中药红花(Carthmus tinctorins)，中医主要用于活血调经，但蒙医药中以古日古木为主药的一些方剂如古日古木-13等为蒙医临床治疗肝脏疾病的常用药物。基于古日古木复方制剂在蒙医临床治疗肝病的良好应用价值，本项目从不同于传统中医药的适应症入手，在体内外研究古日古木单方和复方古日古木-13对实验性肝脏损伤模型的肝脏病理形态学、肝脏生化功能、肝细胞凋亡、重要的细胞再生因子的影响以明确古日古木和以古日古木为主药的蒙药复方是否有确实的肝脏保护作用，对哪些类型的肝损伤作用更好。项目同时研究其JNK信号通路机制，JNK信号通路广泛参与调节细胞凋亡、增殖、代谢、运动及DNA损伤修复等生命过程，其功能的失调被认为与慢性乙型肝炎等多种疾病和病理损伤的发生、发展密切相关。项目对JNK信号通路机制的研究可能找到该类药物治疗作用发挥的重要靶点，也可以为药物的作用提供更加有力的分子水平的依据。

古日古木，即中药红花(Carthmus tinctorins)，中医主要用于活血调经，但蒙医药中以古日古木为主药的一些方剂如古日古木-13等为蒙医临床治疗肝脏疾病的常用药物。本项目从不同于传统中医药的保肝适应症入手，在体内、外研究了古日古木单方和复方古日古木-13对多种实验性肝脏损伤模型的肝脏病理形态学、肝脏生化功能、肝细胞JNK通路的影响。项目研究发现古日古木单、复方对四氯化碳诱导的大鼠急性肝损伤、刀豆蛋白A诱导的小鼠急性自身免疫性肝损伤、大鼠慢性酒精性肝损伤均有一定保护作用，复方高剂量的药物保护作用更好。体外实验研究发现古日古木单复方含药血清处理的肝细胞存活率较损伤细胞有明显增加；体外实验也发现了药物含药血清对脂肪肝细胞的改善作用。项目同时研究其JNK信号通路机制，药物对JNK通路多个靶点有影响，可能是该类药物治疗作用发挥的重要靶点，药物对JNK通路和细胞凋亡的影响也可以为该类药物的作用提供更加有力的分子水平的依据。