Shimoda Terufumi, Obase Yasushi, Matsuse Hiroto, Asai Sadahiro, Iwanaga Tomoaki
Clinical Research Center, Fukuoka National Hospital, Fukuoka, Japan.
Int Arch Allergy Immunol. 2016;171(3-4):276-284. doi: 10.1159/000452709. Epub 2017 Jan 4.
In Japanese patients, alcohol-induced asthma is attributed to elevated plasma concentrations of acetaldehyde following alcohol consumption because of an acetaldehyde dehydrogenase 2 gene (ALDH2) polymorphism. The resulting increase in plasma histamine concentrations seems to trigger the onset of asthma symptoms. However, the specific pathogenic mechanism underlying this response remains unclear. ALDH2-deficient mice were therefore generated to investigate the pathogenesis of alcohol-induced asthma.
ALDH2-deficient mice were generated using embryonic stem cells that were derived from C57BL/6 mice. The resulting mice were backcrossed into the BALB/c mice background. Exon 1 of ALDH2 was replaced with the Neo cassette. Pure ethanol was orally administered to ALDH2-deficient and wild-type mice, and the plasma concentrations of ethanol, acetaldehyde, and histamine, in addition to enhanced pause (Penh) values, were determined and compared between the 2 groups.
We established an ALDH2-deficient mouse line to compare responses between wild-type and ALDH2-deficient mice receiving orally administered ethanol. The results showed that the plasma concentrations of acetaldehyde (p < 0.0001) and histamine (p < 0.005) were significantly higher, and the Penh values (p < 0.01) were significantly greater in the ALDH2-deficient mice, although plasma ethanol levels were not different.
We studied the pathogenesis of alcohol-induced asthma using ALDH2-deficient mice. The results demonstrated that alcohol intake resulted in an increase in acetaldehyde levels, and a subsequent increase in histamine levels, which induced airway constriction. Alcohol consumption is known to be an important factor that exacerbates bronchial asthma, and studies investigating this factor are useful for the treatment of patients with alcohol-induced asthma.
在日本患者中，酒精性哮喘归因于饮酒后由于乙醛脱氢酶2基因（ALDH2）多态性导致血浆乙醛浓度升高。由此导致的血浆组胺浓度升高似乎会引发哮喘症状的发作。然而，这种反应背后的具体致病机制仍不清楚。因此，为了研究酒精性哮喘的发病机制，我们构建了ALDH2缺陷小鼠。
使用源自C57BL/6小鼠的胚胎干细胞构建ALDH2缺陷小鼠。将所得小鼠回交到BALB/c小鼠背景中。用Neo盒替换ALDH2的外显子1。给ALDH2缺陷小鼠和野生型小鼠口服纯乙醇，并测定和比较两组小鼠的乙醇、乙醛和组胺血浆浓度以及增强间歇（Penh）值。
我们建立了一个ALDH2缺陷小鼠品系，以比较口服乙醇的野生型和ALDH2缺陷小鼠的反应。结果显示，尽管血浆乙醇水平没有差异，但ALDH2缺陷小鼠的乙醛（p < 0.0001）和组胺（p < 0.005）血浆浓度显著更高，Penh值（p < 0.01）也显著更大。
我们使用ALDH2缺陷小鼠研究了酒精性哮喘的发病机制。结果表明，饮酒导致乙醛水平升高，随后组胺水平升高，从而诱发气道收缩。众所周知，饮酒是加重支气管哮喘的一个重要因素，对这一因素的研究有助于酒精性哮喘患者的治疗。
