血必净注射液通过调控TGF-β1/Smad3通路改善肺纤维化的作用机制
投稿时间:2025-05-07  修订日期:2025-06-25  点此下载全文
引用本文:肖红科,徐志霞,刘佳,张俊飞,马磊,鲁晓丽,陈中伟.血必净注射液通过调控TGF-β1/Smad3通路改善肺纤维化的作用机制[J].医学研究杂志,2025,54(11):56-62
DOI: 10.11969/j.issn.1673-548X.2025.11.012
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作者单位
肖红科 宁夏医科大学总医院急诊科 银川,750000 
徐志霞 宁夏医科大学总医院急诊科 银川,750000 
刘佳 宁夏医科大学总医院急诊科 银川,750000 
张俊飞 宁夏医科大学总医院急诊科 银川,750000 
马磊 宁夏医科大学总医院急诊科 银川,750000 
鲁晓丽 宁夏医科大学检验学院 银川,750004 
陈中伟 宁夏医科大学总医院急诊科 银川,750000 
基金项目:宁夏自然科学基金资助项目(2023AAC03619,2022AAC03593,2022AAC03211,2021AAC03388);宁夏医科大学校级项目(XM2023047)
中文摘要:目的 探讨血必净注射液(xuebijing injection, XBJ)是否可以通过调控TGF-β1/Smad3通路改善博来霉素(bleomycin,BLM)诱导的肺纤维化。方法 选取18只SD大鼠,采用随机数字表法将其分为3组,即对照组(NC组)、模型组(BLM组)、血必净治疗组(XBJ组),每组各6只。采用苏木精-伊红(hematoxylin-eosin,HE)染色法和Masson染色法观察各组肺纤维化程度,进行肺组织湿干重量比(lung wet-to-dry weight ratio, W/D)及肺系数测定。检测血清中大鼠羟脯氨酸(hydroxyproline,Hyp)、α-平滑肌肌动蛋白(α-smooth muscle actin, α-SMA)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白细胞介素-6(interleukin-6, IL-6)、上皮钙黏蛋白(E-cadherin)、超氧化物歧化酶(superoxide dismutase, SOD)、透明质酸(hyaluronic acid, HA)、转化生长因子-β1(transforming growth factor-β1, TGF-β1)、重组人SMAD家族成员3(mothers against decapentaplegic homolog 3,Smad3)和丙二醛(malondialdehyde, MDA)的表达水平。利用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)法和Western blot法检测肺组织中TGF-β1/Smad3通路关键蛋白和基因的表达情况。结果 与NC组比较,BLM组肺组织出现明显肺泡间隙塌陷、肺泡破坏和紊乱。与BLM组比较,XBJ组肺组织损伤明显缓解。Masson染色结果显示,BLM组胶原纤维沉积明显增加,而XBJ组胶原纤维沉积减少。与NC组比较,BLM组大鼠W/D和肺系数明显升高(P<0.05);而与BLM组比较,XBJ组W/D和肺系数明显降低(P<0.05)。与NC组比较,BLM组血清中TNF-α、IL-6、MDA、Hyp、HA和α-SMA表达水平明显增加,而SOD和E-cadherin表达水平明显降低(P<0.05);与BLM组比较,XBJ组血清中TNF-α、IL-6、MDA、Hyp、HA和α-SMA表达水平明显降低,而SOD和E-cadherin表达水平明显升高(P<0.05)。与NC组比较,BLM组大鼠血清和肺组织中TGF-β1和Smad3蛋白与基因的表达水平明显增加(P<0.05);与BLM组比较,XBJ组大鼠血清和肺组织中TGF-β1和Smad3蛋白与基因的表达水平明显降低(P<0.05)。结论 XBJ可以通过调控TGF-β1/Smad3通路改善BLM诱导的肺纤维化。
中文关键词:血必净注射液 TGF-β1/Smad3通路 肺纤维化
 
Mechanism of Xuebijing Injection in Improving Pulmonary Fibrosis by Regulating TGF-β1/Smad3Pathway.
Abstract:Objective To investigate whether xuebijing injection (XBJ) can improve bleomycin (BLM)-induced pulmonary fibrosis by regulating TGF-β1/Smad3 pathway. Methods Eighteen SD rats were selected and randomly divided into three groups by random number table method:control group (NC group), model group (BLM group), xuebijing treatment group (XBJ group), with 6 rats in each group. Hematoxylin-eosin (HE) and Masson staining were used to observe the degree of pulmonary fibrosis in each group, and the lung wet-to-dry weight ratio (W/D) and lung coefficient were measured. The expression levels of hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), E-cadherin, superoxide dismutase (SOD), hyaluronic acid (HA), transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3) and malondialdehyde (MDA) in serum of rats were detected. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot method were used to detect the expression of key proteins and genes in TGF-β1/Smad3 pathway in lung tissues. ResultsCompared with NC group, the lung tissue of BLM group showed obvious alveolar space collapse, alveolar destruction and disorder. Compared with the BLM group, the lung tissue damage in the XBJ group was significantly alleviated. The results of Masson staining showed that collagen fiber deposition was significantly increased in the BLM group, while that in the XBJ group was decreased. Compared with the NC group, the W/D and lung coefficient of the BLM group were significantly increased (P<0.05); compared with the BLM group, the W/D and lung coefficient of the XBJ group were significantly decreased (P<0.05). Compared with the NC group, the expression levels of TNF-α, IL-6, MDA, Hyp, HA and α-SMA in the serum of the BLM group were significantly increased, while the expression levels of SOD and E-cadherin were significantly decreased (P<0.05); compared with the BLM group, the expression levels of TNF-α, IL-6, MDA, Hyp, HA and α-SMA in the serum of the XBJ group were significantly decreased, while the expression levels of SOD and E-cadherin were significantly increased (P<0.05).. Compared with the NC group, the expression levels of TGF-β1 and Smad3 proteins and genes in the serum and lung tissue of the BLM group were significantly increased (P<0.05); compared with the BLM group, the expression levels of TGF-β1 and Smad3 proteins and genes in the serum and lung tissue of the XBJ group were significantly decreased (P<0.05). Conclusion XBJ can improve BLM-induced pulmonary fibrosis by regulating the TGF-β1/Smad3 pathway.
keywords:Xuebijing injection  TGF-β1/Smad3 pathway  Pulmonary fibrosis
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