二手菸對於倉鼠胎兒所誘發肝損傷之研究

二手菸及煙霧產物是全球公認危害人類健康的因子。暴露在二手菸的環境下會造成心血管疾病及癌症，懷孕的婦女及胎兒也會受到嚴重的傷害。一些研究中顯示孕婦若是暴露在二手菸環境，在剛出生的嬰兒或是出生後的小孩肺部功能都會受到傷害。然而，二手菸對於肝臟的傷害是比較少去探討的。肝臟是一個具有代謝、合成與解毒功能的特別器官。最近的文獻有提到二手菸與非酒精性脂肪肝疾病的關連性，不過卻無提及腹中的胎兒在二手菸的環境中，肝臟受到傷害的反應。 於是本篇實驗我們特別針對二手菸對於胎兒肝臟造成的影響去加以了解，並探討相關的機制。實驗中，使用倉鼠胎兒做為研究的對象，在second-hand smoke的傷害下，以gelatin zymography及western blot去分別觀察倉鼠胎兒肝臟中蛋白的表現情形，結果發現經由二手菸的暴露可以明顯的增加肝臟中MMP-9、CRP、iNOS等發炎因子的釋放，以及細胞激素IL-1β的產生，進而增加發炎反應，也可以經由P38、AKT及ERK 等訊息路徑去活化NF-κB而調節發炎反應，顯著的增加細胞脂質過氧化、ROS傷害的程度，使肝臟中免疫發炎反應進行。同時，也可使肝細胞藉由p53/21蛋白的表現進而誘發肝細胞凋亡。二手菸使體內氧化壓力的增加，進而使肝臟脂質堆積，這在疾病分類上屬非酒精性的脂肪肝疾病。目前非酒精性脂肪肝疾病在臨床上並無有效的藥物可供治療。所以，觀察倉鼠胎兒肝臟發炎的訊息路徑，未來或許可找出治療方法，來減少二手菸對於胎兒肝臟的傷害。

Second-hand smoke and tobacco smoke products are recognized global risks for human health. It can cause cardiovascular disease and cancer that exposure of second- hand smoke, especially pregnant women and fetus. Several studies have shown an effect of second hand smoke exposure during pregnancy upon lung function in the newborn infant and after birth. However, it is less explored that the liver damage of second-hand smoke exposure. The liver is an exceptional organ in terms of its metabolic, synthetic, and detoxifying function. Recent reports has referred the relationship between second-hand smoke and non-alcoholic fatty liver disease, but not include the liver damage in fetus. In our experiment, we want to understand affect and explore mechanism about that the fetal liver exposure of second-hand smoke. Experimentally, using hamster fetus, in the injury of secondhand smoke treatment , respectively by gelatin zymography and Western blot observation of hamster fetus liver protein expression in case. The results showed that exposure of second- hand smoke can increase the release of MMP-9, CRP, iNOS , other inflammatory factors and IL-1β in the liver, and lead to increase inflammatory response. It can also be NF-κB activation through P38, AKT and ERK signaling pathways to regulate the inflammatory response,. As well as a significant increase in cell lipid peroxidation and ROS injury degree , so that the immune inflammatory reaction of liver in progress. Meanwhile, the second-hand smoke also can make liver cells to induce apoptosis by the performance of p53/21 protein, and increase oxidative stress thereby enabling the liver lipid accumulation. It belongs to non-alcoholic fatty liver disease in diseases classification . There is no effective drug available for treatment in clinical practice. Therefore, observe inflammation message path of hamster fetal liver. So future we can find a treatment method and reduce second-hand smoke damage to the fetal liver.