| 摘要: |
| 目的：探讨水仙环素对高氧诱导新生大鼠急性肺损伤的影响及其机制。方法：取足月新生Wistar大鼠40只，随机分为常氧组（21% O2）、常氧+水仙环素组、高氧组（85% O2）、高氧+水仙环素组，每组10只。各组大鼠于不同含氧量条件下暴露7 d，另取足月新生大鼠50只，随机分为常氧组、高氧组、高氧+水仙环素组、高氧+水仙环素+蛋白激酶B（AKT）抑制剂组及高氧+水仙环素+雷帕霉素组，每组10只。各药物组于出生后0、2、4、6 d时分别腹腔注射1 mg/kg水仙环素、1mg/kg AKT抑制剂和4mg/kg雷帕霉素，比较各组大鼠肺损伤、促炎细胞因子、纤维化及肺组织细胞凋亡水平。结果：与常氧组比较，高氧组大鼠体质量、肺组织B淋巴细胞瘤-2基因/Bcl-2相关X蛋白（Bcl-2/Bax）水平明显降低，支气管肺泡灌洗液（BALF）中细胞总数、总蛋白及肺组织湿干质量、BALF与血清中肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、单核细胞趋化因子（MCP-1）、IL-6含量、肺组织α平滑肌动蛋白（α-SMA）、波形蛋白及胶原蛋白Ⅰ表达、肺组织细胞凋亡率、原代肺成纤维细胞凋亡率、磷酸化蛋白激酶B（p-AKT）/AKT、磷酸化雷帕霉素靶蛋白（p-mTOR）/mTOR升高（P<0.05）；常氧组与常氧+水仙环素组上述指标比较差异无统计学意义（P>0.05）。与高氧组比较，高氧+水仙环素组体质量、肺组织Bcl-2/Bax水平升高，BALF中细胞总数、总蛋白及肺组织湿/干质量、BALF与血清中TNF-α、IL-1β、MCP-1、IL-6含量、肺组织α-SMA、波形蛋白及胶原蛋白Ⅰ表达、肺组织细胞凋亡率、原代肺成纤维细胞凋亡率、p-AKT/AKT、p-mTOR/mTOR降低（P<0.05）。与高氧+水仙环素组比较，高氧+水仙环素+AKT抑制剂组TNF-α、IL-1β水平升高（P<0.05），高氧+水仙环素+雷帕霉素组TNF-α、IL-1β、胶原蛋白Ⅰ表达升高，Bcl-2/Bax水平明显降低（P<0.05）。结论：水仙环素可保护新生大鼠高氧肺损伤，其机制可能与水仙环素活化AKT/mTOR信号通路，改善炎症反应、减缓肺纤维化程度、抑制肺组织细胞的凋亡有关 |
| 关键词: 急性肺损伤 水仙环素 蛋白激酶B/雷帕霉素靶蛋白信号通路 肺纤维化 凋亡 |
| DOI：10.13407/j.cnki.jpp.1672-108X.2022.07.001 |
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| 基金项目:河南省医学科技攻关计划项目,编号201803784 |
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| Narciclasine-Activated AKT/mTOR Pathway in Alleviating Hyperoxia-Induced Acute Lung Injury in Neonatal Rats |
| Han Xu, Zhu Ping, Liu Ni, Wu Zongyue, Yang Jing |
| (Nanyang Central Hospital, Henan Nanyang 473001, China) |
| Abstract: |
| Objective: To explore the effects and mechanism of narciclasine on hyperoxia-induced acute lung injury in neonatal rats. Methods: A total of 40 full-term neonatal Wistar rats were randomly divided into the normoxia group (21% O2), normoxia+narciclasine group, hyperoxia group (85% O2, hyperoxia) and hyperoxia+narciclasine group, with 10 cases in each group. Rats in all groups were exposed under conditions of different oxygen contents for 7 d. Other 50 full-term neonatal rats were randomly divided into the normoxia group, hyperoxia group, hyperxia+narciclasine group, hyperoxia+narciclasine+protein kinase B (AKT) inhibitor group and hyperoxia+narciclasine+rapamycin group, with 10 cases in each group. All drug therapy groups were intraperitoneally injected with 1 mg/kg narciclasine, 1 mg/kg AKT inhibitor and 4 mg/kg rapamycin at 0, 2, 4 and 6 d after birth, respectively. The levels of lung injury, pro-inflammatory cytokines, fibrosis and lung tissue apoptosis among all groups were compared. Results: Compared with the normoxia group, body mass and levels of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) in lung tissues decreased significantly in the hyperoxia group, total number of cells in bronchoalveolar lavage fluid (BALF), total protein, wet and dry weight of lung tissues, levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1) and IL-6 in BALF and serum, expressions of α smooth actin (α-SMA), vimentin and collagen Ⅰ in lung tissues, apoptosis rate of lung tissues, fibroblast apoptosis rate of primary lung, phosphorylated protein kinase B (p-AKT)/AKT and phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR increased significantly (P<0.05), and there was no significant change in the above indicators between the normoxia group and the normoxia+narciclasine group (P>0.05). Compared with the hyperoxia group, body mass and Bcl-2/Bax levels in lung tissues increased significantly in the hyperoxia+narciclasine group, total number of cells in BALF, total protein, wet and dry weight of lung tissues, levels of TNF-α, IL-1β, MCP-1 and IL-6 in BALF and serum, expressions of α-SMA, vimentin and collagen Ⅰ in lung tissues, apoptosis rate of lung tissues, fibroblast apoptosis rate of primary lung, p-AKT/AKT and p-mTOR/mTOR decreased significantly (P<0.05). Compared with the hyperoxia+narciclasine group, levels of TNF-α and IL-1β increased significantly in the hyperoxia+narciclasine+AKT inhibitor group (P<0.05), levels of TNF-α, IL-1β and expressions of collagen Ⅰ increased significantly in the hyperoxia+narciclasine+rapamycin group, and the levels of Bcl-2/Bax decreased significantly (P<0.05). Conclusion: Narciclasine can protect neonatal rats from hyperoxia-induced lung injury. The mechanism may be related to that narciclasine can activate AKT/mTOR signaling pathways, improve the inflammation response, relieve the lung fibrosis and inhibit the apoptosis of lung tissues. |
| Key words: acute lung injury narciclasine protein kinase B/mammalian target of rapamycin signaling pathway lung fibrosis apoptosis |
