目的 探讨汉防己甲素对多壁碳纳米管联合脂多糖诱导的小鼠肺结节病模型的保护作用及机制。方法 将C57BL/6小鼠随机分为对照组、模型组、汉防己甲素（19.5、39.0、78.0 mg/kg）组，每组10只。采用苏木精–伊红染色观察肺组织病理形态，免疫组化检测CD3⁺ T淋巴细胞和F4/80⁺巨噬细胞浸润，BCA法检测支气管肺泡灌洗液（BALF）中总蛋白含量，显色法检测乳酸脱氢酶（LDH）活性，酶联免疫吸附测定（ELISA）法检测BALF中白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）含量及血清中可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、骨桥蛋白（OPN）水平，Western blotting检测肺组织中E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、ICAM-1、VCAM-1蛋白表达。结果 与模型组相比，汉防己甲素78.0 mg/kg组肺组织肉芽肿数量、肉芽肿面积占比、肺损伤评分显著降低（P＜0.05）；汉防己甲素39.0、78.0 mg/kg组肺组织中CD3⁺阳性面积百分比、F4/80阳性面积百分比均显著下降（P＜0.01、0.001）。与模型组相比，汉防己甲素各剂量组sICAM-1含量及N-cadherin、VCAM-1蛋白表达显著下降（P＜0.05、0.01、0.001）。与模型组相比，汉防己甲素39.0、78.0 mg/kg组小鼠BALF中总蛋白、TNF-α含量及血清sVCAM-1、OPN水平均显著降低（P＜0.05、0.01、0.001）；汉防己甲素78.0 mg/kg组小鼠BALF中LDH、IL-1β、IL-6含量及ICAM-1表达蛋白表达显著降低，E-cadherin蛋白表达显著升高（P＜0.05、0.01）。肺组织黏附分子表达水平与CD3⁺ T细胞及F4/80⁺巨噬细胞浸润程度呈正相关。结论 汉防己甲素对多壁碳纳米管联合脂多糖诱导的小鼠肺结节病具有明确保护作用，其保护作用可能与下调ICAM-1、VCAM-1等黏附分子表达、抑制炎症细胞浸润及减轻局部炎症反应相关。

Objective To investigate the protective effect and mechanism of tetrandrine on a mouse model of pulmonary sarcoidosis induced by multi-walled carbon nanotubes combined with lipopolysaccharide. Methods C57BL/6 mice were randomly divided into control group, model group, and tetrandrine (19.5, 39.0, and 78.0 mg/kg) groups, with 10 mice in each group. HE staining was used to observe the pathological morphology of lung tissue; immunohistochemistry was used to detect CD3⁺ T lymphocyte and F4/80⁺ macrophage infiltration, BCA assay was used to detect total protein content in BALF, colorimetric assay was used to detect LDH activity, ELISA was used to detect the levels of IL-1β, IL-6, TNF-α, and IFN-γ in BALF, as well as serum levels of sICAM-1, sVCAM-1, and OPN. Western blotting was used to detect the protein expression of N-cadherin, E-cadherin, ICAM-1, and VCAM-1 in lung tissue. Results Compared with the model group, the number of granulomas, the proportion of granuloma area, and the lung injury score in the tetrandrine 78.0 mg/kg group were significantly reduced (P < 0.05). Percentages of CD3⁺ positive area and F4/80 positive area in the lung tissue in the tetrandrine 39.0 and 78.0 mg/kg groups were significantly decreased (P < 0.01, 0.001). Compared with the model group, the contents of sICAM-1 and the protein expressions of N-cadherin and VCAM-1 in each dose group of tetrandrine were significantly decreased (P < 0.05, 0.01, 0.001). Compared with the model group, the total protein, TNF-α content in BALF and the levels of sVCAM-1 and OPN in serum in the tetrandrine 39.0 and 78.0 mg/kg groups were significantly decreased (P < 0.05, 0.01, 0.001). The contents of LDH, IL-1β, IL-6 in BALF, and the protein expression of ICAM-1 in the tetrandrine 78.0 mg/kg group were significantly decreased, while the protein expression of E-cadherin was significantly increased (P < 0.05, 0.01). The expression levels of adhesion molecules in lung tissue were positively correlated with the infiltration degree of CD3⁺ T cells and F4/80⁺ macrophages. Conclusion Tetrandrine exerts a definite protective effect against multi-walled carbon nanotubes combined with lipopolysaccharide-induced pulmonary sarcoidosis in mice, which may be associated with downregulating the expression of adhesion molecules such as ICAM-1 and VCAM-1, inhibiting inflammatory cell infiltration, and alleviating local inflammatory responses.

R286.4

中国中医科学院科技创新工程项目（CI2026A04618）；解放军总医院第六医学中心创新培育基金资助项目（CXPY202406）；中国中医科学院中药研究所中央级公益性科研院所基本业务费专项资金资助（ZXKT22045，ZXKT25006）；中国中医科学院优秀青年科技人才培养专项（ZZ16-YQ-027）