解剖学杂志2023，Vol.46Issue(5)：379-384,后插1,7.DOI:10.3969/j.issn.1001-1633.2023.05.003
骨化三醇通过B细胞受体/PI3K/AKT/NF-κB通路抑制大鼠高原肺水肿的发生
Calcitriol inhibits B-cell receptor/PI3K/AKT/NF-κB pathway to improve high altitude pulmonary edema in rats
摘要
Abstract
Objective:To investigate the mechanism of which calcitriol improves high altitude pulmonary edema(HAPE)in rats by inhibiting the B-cell receptor/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/nuclear factor-κB(NF-κB)pathway.Methods:Male SD rats were randomly divided into normoxia,hypoxia,and hypoxia+calcitriol groups(0.252 μg/kg).After continuous gavage administration for 5 days,except for the normoxia group,the other two groups were placed under simulated hypoxic stress at an altitude of 6 000 m for 48 h to establish the HAPE rat model.Lung water content was determined and measured by dry and wet specific gravity methods;H-E staining was performed to observe the pathological changes of lung tissue and inflammation score;TUNEL method was used to detect apoptosis in lung tissue;ELISA was used to detect B cell activating factor(BAFF),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interferon-γ(IFN-γ),interleukin-4(IL-4)and interleukin-10(IL-10)in lung tissue;immunofluorescence staining was used to observe the expression of CD21 and IκBα in lung tissue;Western blotting was performed to detect the expression of PI3K,p-PI3K,AKT,p-AKT,NF-κB inhibitor α(IκBα)and p-IκBα in lung tissues.Results:Compared with the normoxic group,slight alveolar septal widening and inflammatory cell infiltration were seen in lung tissue.Lung water content,lung tissue apoptosis,the content of BAFF,TNF-α,IL-6,IFN-γ and the expression of CD21,p-PI3K,p-AKT were significantly increased.The content of IL-4,IL-10 and the expression of IκBα,p-IκBα were significantly decreased in lung tissue in the hypoxic group.Compared with the hypoxic group,inflammatory cell infiltration was reduced;lung water content,lung tissue apoptosis,BAFF,TNF-α,IL-6,IFN-γ content and CD21,p-PI3K,p-AKT expression were significantly decreased;IL-4,IL-10 content and IκBα,p-IκBα expression in lung tissue were significantly increased in the hypoxic+calcitriol group.Conclusion:Calcitriol can inhibit HAPE inflammatory response,and its mechanism of action may be related to the inhibition of B-cell receptor/PI3K/AKT/NF-κB signaling pathway.关键词
高原肺水肿/骨化三醇/肺/B细胞受体/磷脂酰肌醇3激酶/蛋白激酶/核因子-κB信号通路Key words
high altitude pulmonary edema/lung/calcitriol/B-cell receptor/phosphatidylin-ositol-3-kinase/serine-threonine kinase/nuclear factor-κB signaling pathway引用本文复制引用
戴重阳,林雪,王雅轩,吕中奎,朱梦婷,邓章昌,蒲小燕..骨化三醇通过B细胞受体/PI3K/AKT/NF-κB通路抑制大鼠高原肺水肿的发生[J].解剖学杂志,2023,46(5):379-384,后插1,7.基金项目
国家自然科学基金(82160322) （82160322）
青海省财政科研项目基金(2023-ZJ-746) （2023-ZJ-746）
