机构地区:[1]福建省癌症与神经退行性疾病转化研究重点实验室,福建医科大学基础医学院,福州350122 [2]福建省肿瘤转化医学重点实验室,莆田学院基础医学院,福建莆田351100
出 处:《解剖学报》2025年第2期232-238,共7页Acta Anatomica Sinica
基 金:福建省教育厅中青年教师教育科研项目(JAT220284)。
摘 要:目的探讨姜黄素Ⅰ(CurⅠ)减轻博来霉素(BLM)诱导导致的小鼠肺纤维化的作用及机制。方法将C57BL/6小鼠随机分成3组(每组6只):正常(normal)组,一次性气管内滴注生理盐水;BLM组,一次性气管内滴注BLM(3 mg/kg)制备肺纤维化模型;BLM+CurⅠ组,同BLM组处理后,腹腔注射姜黄素Ⅰ(200μg/kg,Bid×14 d)。各组小鼠在实验第14天后处死,并收集肺、血浆、肺泡灌洗液。通过组织病理学、肺泡炎症和肺纤维化程度评分,分析姜黄素Ⅰ对肺纤维化小鼠核模型肺结构的影响;免疫组织化学染色、Western blotting和Real-time PCR分析姜黄素Ⅰ对肺纤维化小鼠核因子(NF)-κB通路相关蛋白表达的影响,ELISA分析姜黄素Ⅰ对肺纤维化小鼠血清和肺泡灌洗液中炎症因子的影响。结果与BLM组比,姜黄素Ⅰ干预可明显减轻小鼠肺组织的损伤。与normal组比,BLM组小鼠血清中白细胞介素(IL)-6、肺泡灌洗液IL-1β、IL-6表达水平显著升高(P<0.001),BLM+CurⅠ组小鼠血清中IL-6、肺泡灌洗液IL-1β、IL-6表达水平明显下降(P<0.05)。与normal组比,BLM组NF-κB、CD54、生长调节致癌基因(GRO)、CD11b蛋白表达明显上调(P<0.05),BLM+CurⅠ组小鼠肺组织中NF-κB和CD54的蛋白水平明显下降(P<0.05),CD11b、GRO也呈下降趋势。结论姜黄素Ⅰ能够抑制肺纤维化小鼠体内的炎症反应,改善小鼠肺纤维化,其机制可能与抑制NF-κB/CD54信号通路有关。Objective To explore the effects and mechanisms of curcuminⅠ(CurⅠ)in alleviating bleomycin(BLM)induced pulmonary fibrosis in mice.Methods C57BL/6 mice were randomly divided into 3 groups(n=6 per group),normal group received a single intratracheal instillation of saline;BLM group received a single intratracheal instillation of BLM(3 mg/kg)to induce pulmonary fibrosis;BLM+CurⅠgroup received intraperitoneal injections of curcuminⅠ(200μg/kg,Bid×14 day)in addition to BLM treatment.Mice from each group were euthanized on day 14 of the experiment,and lungs,plasma,and bronchoalveolar lavage fluid were collected.Histopathological examination,scoring of pulmonary inflammation and fibrosis were performed to analyze the effects of curcuminⅠon nuclear lung structure in the pulmonary fibrosis mouse model.Immunohistochemistry,Western blotting,and Real⁃time PCR were conducted to assess the impact of curcuminⅠon nuclear factor(NF)⁃κB pathway⁃related protein expression in the pulmonary fibrosis mouse model.ELISA was used to evaluate the effects of curcuminⅠon inflammatory factors in serum and bronchoalveolar lavage fluid of the pulmonary fibrosis mice.Results Compared to the BLM group,intervention with curcuminⅠsignificantly alleviated lung tissue damage in mice.Compared to the normal group,mice in the BLM group showed significantly elevated levels of interleukin(IL)⁃6 in serum and IL⁃1β,IL⁃6 in bronchoalveolar lavage fluid(P<0.001).In contrast,mice in the BLM+CurⅠgroup exhibited significant decreases in serum IL⁃6 and IL⁃1β,as well as IL⁃6 expression in bronchoalveolar lavage fluid(P<0.05).Compared to the normal group,protein expression levels of NF⁃κB,CD54,growth regulated oncogene(GRO),and CD11b were significantly upregulated in the BLM group(P<0.05).In contrast,protein levels of NF⁃κB and CD54 were significantly decreased in lung tissues of mice from the BLM+CurⅠgroup(P<0.05),with CD11b and GRO also showing a decreasing trend.Conclusion CurcuminⅠcan suppress inflammation in pu
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