HERBAL REMEDIES AND THE TREATMENT OF LIVER DISEASE

成功的治疗肝损伤和肝纤维化的方法应该包括使用廉价、无毒的药物，这些药物将合理地处理导致肝脏疾病的病理生理过程。目前，在我们的标准治疗性医疗机构中还没有这样的药物。然而，在亚洲国家，以草药形式存在的替代治疗剂已经被用于治疗肝病几代人了。因此，我们的目标是采用严格的科学方法，调查一些草药的有效性，以确定这些药物的相对有效性以及它们可能抑制肝损伤和肝纤维化的机制。具体目的：1)确定中药在体外肝细胞损伤模型中的作用；2)确定中药对三种肝损伤和肝纤维化模型的作用。方法：用乙醇、叔丁基过氧化氢(TBHP)或四氯化碳(CC14)处理成骨障碍Shionogi大鼠的肝细胞和Kupffer细胞，观察其损伤和激活过程。通过脂质过氧化、细胞因子合成、组织转谷氨酰胺酶(TTG)表达和核因子-kappaB结合活性的测定，将探讨草药抑制这种损伤过程的机制。在活体系统中，还将使用中药药物来抑制CC14给药和胆管结扎所致的损伤和纤维化，其作用效果将通过组织学和胶原蛋白测定、tTG表达的免疫组织化学和NF-kappaB激活的凝胶抑制分析来确定。与健康相关：在这些肝损伤和纤维化模型中成功使用一种或多种草药将为在人类肝病的一系列临床试验中使用这些廉价、无毒的药物提供合理的基础。

A successful approach to the therapy of hepatic injury and fibrosis should ideally involve the employment of inexpensive, non-toxic agents that will address rationally the pathophysiological processes that are responsible for the liver disease. At present no such agents are available in our standard therapeutic armamentarium. However, alternative therapeutic agents, in the form of herbal remedies, have been employed for generations in Asian countries in the treatment of liver diseases. Thus, our objective is to investigate the effectiveness of a number of herbal remedies, employing a rigorous scientific approach, to determine the relative effectiveness of these agents and the mechanisms by which they may be inhibiting liver injury and fibrosis. Specific Aims: 1) To determine the effectiveness of the herbal medicines in in vitro models of liver cell injury; and 2) to ascertain the effect of the herbal medicines on three models of liver injury and fibrosis. Methods: Hepatocytes and Kupffer cells from Osteogenic Disorder Shionogi (ODS) rats will be treated with ethanol, tert- butyl hydrogen peroxide (TBHP), or CC14 to characterize the injury and activation process. Mechanisms whereby herbal remedies inhibit this injury process will be explored by assays of lipid peroxidation, cytokine synthesis, tissue transglutaminase (tTG) expression, and NF-kappaB binding activity. Herbal remedies will also be employed to inhibit the injury and fibrosis induced by CC14 administration and bile duct ligation in in vivo systems, and the effectiveness of their action will be determined by histology and collagen protein determination, immunohistochemistry of tTG expression, and gel retardation assays of NF-kappaB activation. Health Relatedness: The successful use of one or more of the herbal agents in these models of liver injury and fibrogenesis will provide a rational basis for the use of these inexpensive, non-toxic agents in a series of clinical trials of liver disease in humans.