| 引用本文: | 李小兵,王梅芳,程雪琴,王淑惠,唐以军.异甘草素通过降低凋亡缓解SiNPs诱导的矽肺炎症与纤维化[J].中国现代应用药学,2025,42(6):33-40. |
| LI Xiaobing,WANG Meifang,CHEN Xueqin,WANG Shu-hui,TANG Yijun.Isoliquiritigenin alleviates SiNPs-induced pulmonary inflammation and fibrosis by inhibiting apoptosis[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(6):33-40. |
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| 摘要: |
| 目的 探讨异甘草素（isogliquiritin，ISL）对纳米二氧化硅（silica nanoparticles，SiNPs）诱导的矽肺纤维化的影响及其分子机制。方法 将C57BL/6J小鼠随机分为5组：对照组、模型组、ISL低剂量组（5mg·kg?1）、ISL中剂量组（10mg·kg?1）、ISL高剂量组（20mg·kg?1）。构建SiNPs诱导小鼠矽肺模型，矽肺小鼠经过干预后，通过HE和Masson染色观察各组肺组织炎症和肺组织纤维化程度；免疫组化检测肺纤维化相关蛋白α-平滑肌肌动蛋白（alpha-smooth muscle actin, α-SMA）和胶原蛋白Ⅰ型（collagen type I, Collagen Ⅰ）的表达。为进一步探讨ISL对SiNPs诱导矽肺纤维化潜在的分子机制，免疫组化和Western blot法检测肺组织凋亡相关蛋白Bax、Caspase-3；构建SiNPs刺激A549细胞模型，MTT法检测SiNPs和ISL对A549细胞存活率；流式细胞仪FITC-Annexin V/PI荧光染色法检测细胞凋亡率变化；Western blot实验检测细胞凋亡蛋白Bax、Caspase-3的表达。结果 在体内，HE和Masson染色结果显示ISL的干预显著改善SiNPs诱导的小鼠肺损伤和胶原纤维沉积（P＜0.01）；显著抑制α-SMA和Collagen Ⅰ蛋白的表达（P＜0.01），同时降低凋亡相关蛋白Bax、Caspase-1的表达（P＜0.05）。在体外，ISL提高细胞的存活率（P＜0.01），同时抑制SiNPs诱导的细胞凋亡率和凋亡相关蛋白Bax、Caspase-3的表达（P＜0.05）。结论 ISL通过抑制抑制细胞凋亡缓解SiNPs诱导的肺部炎症与纤维化，为临床治疗矽肺纤维化提供新思路。 |
| 关键词: 矽肺 SiNPs 肺纤维化 异甘草素 凋亡 |
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| 基金项目:湖北省卫生健康委科研资助（WJ2023M167）；湖北省自然科学基金（2022CFB028）；湖北省医学领军人才 |
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| Isoliquiritigenin alleviates SiNPs-induced pulmonary inflammation and fibrosis by inhibiting apoptosis |
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LI Xiaobing,WANG Meifang,CHEN Xueqin,WANG Shu-hui,TANG Yijun
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1.Department of Respiratory and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine,;2.Hubei University of Medicine
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| Abstract: |
| OBJECTIVE To investigate the effect of isogliquiritin (ISL) on silicosis fibrosis induced by silica nanoparticles (SiNPs) and its molecular mechanism. METHODS C57BL/6J mice were randomly divided into 5 groups: control group, model group, ISL low-dose group (5 mg·kg?1), ISL medium-dose group (10 mg·kg?1) and ISL high-dose group (20 mg·kg?1). A mouse silicosis model induced by SiNPs was established. After intervention with ISL, Hematoxylin-eosin (HE) and Masson staining were used to observe the degree of pulmonary inflammation and pulmonary fibrosis. The expression of fibrosis-associated (alpha-smooth muscle actin) α-SMA and (collagen type I) Collagen I was detected by immunohistochemistry. To explore the potential molecular mechanism of ISL, The apoptosis-related proteins Bax and Caspase-3 were detected by immunohistochemistry and Western blot. The A549 cell model stimulated by SiNPs was constructed. The survival rate of A549 cells was determined by MTT. The cells apoptosis rate was detected by flow cytometry FITC-Annexin V/PI fluorescence staining. The expressions of apoptotic proteins Bax and Caspase-3 were detected by Western blot. RESULTS In vivo, The results of HE and Masson staining showed that ISL intervention significantly improved SiNPs-induced lung injury and collagen fiber deposition (P<0.01). The expressions of α-SMA and Collagen I proteins were significantly inhibited (P<0.01), while the apoptosis-related proteins Bax and Caspase-1 expression were decreased (P<0.05). In vitro, ISL increased cell survival and decreased SiNPs-induced apoptosis (P<0.01), inhibited the expressions of apoptosis-related proteins Bax and Caspase-3 (P<0.05). CONCLUSION ISL alleviates SiNPs-induced pulmonary inflammation and fibrosis by inhibiting apoptosis, which provided a new idea for clinical treatment of silicosis fibrosis. |
| Key words: silicosis siNPs pulmonary fibrosis Isoliquiritigenin apoptosis |
