囊性纤维化(CF)是高加索人最常见的常染色体隐性遗传病,影响全球超过10万人。它是由编码CFTR的基因中的致病变异引起的,上皮和其他细胞质膜上的阴离子通道。许多CF致病变体破坏CFTR的生物合成和运输或降低其离子通道功能。最常见的突变,在位置508(F508del)失去苯丙氨酸,导致错误折叠,保留在内质网中,和蛋白质的过早降解。可用于治疗CF肺病的疗法包括抗生素,粘液溶解剂,支气管扩张剂,物理治疗,和最近的CFTR调制器。迄今为止,目前还没有找到治愈这种缩短寿命的疾病的方法。三联联合药物治疗,TRIKAFTA®,由三种药物组成:Elexacaftor(VX-445),Tezacaftor(VX-661)和Ivacaftor(VX-770)。这种疗法,受益于CF的人,提高体重,肺功能,能量水平(由减少的疲劳定义),和整体生活质量。我们在显示与人CF相关的肺异常的F508deltm1EUR小鼠模型中检查了LAU-7b口服治疗和三联疗法组合对肺功能的影响。我们评估了肺功能,肺组织病理学,蛋白质氧化,脂质氧化,F508deltm1EUR小鼠的脂肪酸和脂质分布。
Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.