ADENO ASSOCIATED VIRAL GENE DELIVERY AND OXIDATIVE STRES

酒精诱导的肝损伤主要归因于氧化应激，最有可能是由于缺血/再灌注损伤;然而，涉及的确切机制仍不清楚。此外，酒精与抗氧化保护的降低相关;因此，假设通过重组腺相关病毒（rAAV）递送抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶将保护免受氧化应激。 为了检验这一假设，SOD和过氧化氢酶将通过腺病毒和腺相关病毒递送，并将在缺血/再灌注模型以及酒精性肝病的临床相关Tsukamoto-French肠内喂养模型中评估其对氧化损伤的保护作用。 此外，氧化应激已被认为增加rAAV体外转导。 因此，我们将测试由慢性乙醇引起的氧化应激将增加体内rAAV转导的假设。 由于酒精性肝病是一种流行的，毁灭性的疾病，这是这项工作的目标，以获得新的见解酒精性肝损伤的机制，并提供令人兴奋的新方法，为临床应用。

Alcohol-induced liver injury can be attributed largely to oxidative stress, most likely due to ischemia/reperfusion injury; however, the exact mechanisms involved are still unknown. Additionally, alcohol is associated with a decrease in anti- oxidant protection; therefore, it is hypothesized that delivery of antioxidant enzymes superoxide dismutase (SOD) and catalase via recombinant adeno-associated virus (rAAV) will be protective against oxidative stress. To test this hypothesis, SOD and catalase will be delivered via adenovirus and adeno-associated virus and will be assessed for protection against oxidative injury in ischemia/reperfusion models as well as in the clinically relevant Tsukamoto-French enteral feeding model of alcoholic liver disease. Furthermore, oxidative stress has been suggested to increase rAAV transduction in vitro. Therefore, we will test the hypothesis that oxidative stress caused by chronic ethanol will increase rAAV transduction in vivo. Because alcohol-induced liver disease is a prevalent, devastating disease, it is the objective of this work to gain new insight into the mechanism of alcohol-induced liver injury, and to provide exciting new approaches for clinical application.