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低剂量乙醇对糖尿病诱导的肺损伤中 NLRP3 炎性小体的影响。

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury.

机构信息

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical College; 287 Changhuai Road, Anhui 233004, P.R. China.

Department of Tuberculosis, the Second Hospital of Nanjing, Affiliated Hospital of Nanjing University of Chinese Medicine, 1-1 Zhongfu Road, Jiangsu 210000, P.R. China.

出版信息

Exp Anim. 2021 Aug 6;70(3):364-371. doi: 10.1538/expanim.20-0123. Epub 2021 Apr 2.

Abstract

To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

摘要

观察 NLR 家族包含 pyrin 结构域 3(NLRP3)炎症小体在糖尿病诱导的肺损伤大鼠模型中的变化,并研究低剂量乙醇对 NLRP3 炎症小体产生的影响。建立 1 型糖尿病(DM)大鼠模型,将大鼠分为 4 组:正常对照组(CON 组)、低剂量乙醇组(EtOH 组)、糖尿病组(DM 组)和糖尿病+乙醇组(DM+EtOH 组)。分别喂养 6 和 12 周后,计算肺湿重/体重比(肺/体系数),并通过 HE 和 Masson 染色观察肺形态和纤维化变化。电镜观察肺超微结构变化。Western blot 检测线粒体乙醛脱氢酶 2(ALDH2)和 NLRP3 炎症小体关键因子 NLRP3、ASC 和 caspase-1 蛋白的变化。与 CON 组相比,DM 组肺/体系数增加(P<0.05),出现肺纤维化,ALDH2 蛋白表达降低,NLRP3、ASC 和 caspase-1 蛋白表达增加(P<0.05)。与 DM 组相比,DM+EtOH 组肺/体系数和纤维化程度降低,ALDH2 蛋白表达增加(P<0.05),NLRP3、ASC 和 caspase-1 蛋白表达降低(P<0.05)。因此,低剂量乙醇通过增加 ALDH2 蛋白表达抑制 NLRP3 炎症小体的产生,减轻糖尿病诱导的肺损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb28/8390306/024794cf74d3/expanim-70-364-g001.jpg

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