关键词:

哮喘,  , 中性粒细胞,  , 1, 25?二羟维生素D3,  , 内质网应激,  , 核因子E2相关因子

Abstract:

Objective To investigate the therapeutic effect of 1，25⁃dihydroxyvitamin D3 on neutrophilic asthma inmice，as well asits influence on Nrf2 expression and endoplasmic reticulum stress state. Methods Twenty⁃ four female Balb/c mice were randomly divided into 3 groups：normal control group（A），neutrophilic asthma model group（B）and 1，25（OH）2D3 treatment group（C），with eight mice in each group.A mouse model of neutrophilic asthma was established by the method of CFA+OVA（complete Freund′s adjuvant，chicken ovalbumin）. Group C was given 0.1% intraperitoneal injection of 1，25（OH）2D3（4 μg·kg⁃1）before each challenge by intranasal instillation of OVA.A non⁃invasive airway reactivity test was performed，as well as lung tissue samples and bronchoalveolar lavage fluid（BALF）. The inflammatory changes in lung tissue were observed using pathological HE staining. BALF inflammatory cells were counted and classified，and levels of IL⁃4，IL⁃17，IL⁃5，CXCL2 and CXCL8 were mea⁃ sured. Ly ⁃6G immunohistochemistry staining was performed to better understand neutrophil infiltration in lung tissue. Western blot was used to determine the protein expression of CHOP，GRP78，and Nrf2 in lung tissue. GSH，MDA concentration in lung tissue，and NQO1 mRNA levels were all found to be elevated. Results The levels of various cytokines in BALF in the 1，25（OH）2D3 treatment groupwere significantly lower than in the model group （P < 0.05），as was the proportion of neutrophils in BALF. Lung histology revealed that the treatment group had less airway inflammation than the model group.When compared to the model group，the protein levels of CHOP and GRP78 in the treatment group were significantly lower，the protein level of Nrf2 was higher，and the expression level of NQO1 mRNA was higher（P < 0.05）. Conclusion 1，25⁃Dihydroxyvitamin D3 reduces airway inflammation in neutrophilic asthmatic mice by increasing the expression of the Nrf2 protein，inhibiting endoplasmic reticulum stress，and inhibiting the secretion of inflammatory cytokines.

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