Wang Bo-Han, Yu Ke-Yao, Zhang Xiao-Na, Sun Xian-Hong, Tang Ling-Ling, Shi Xiao-Lu
NanJing JiangNing Hospital of Chinese Medicine/Affiliated jiangning Hospital of Chinese Medicine, China Pharmaceutical University, Nanjing, Jiangsu, 210029, People's Republic of China.
Affiliated Hospital of Nanjing University of Chinese Medicine/ Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, 210029, People's Republic of China.
J Inflamm Res. 2025 Jan 22;18:1053-1065. doi: 10.2147/JIR.S480112. eCollection 2025.
To evaluate the effects of Fu Tu Sheng Jin Rehabilitation Formula (FTSJRF) on airway inflammation, mucus secretion, and immunoreaction in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-induced mouse model.
Forty-two mice were randomly divided into seven groups: normal, D1, D3, D10, D10H, D10M and D10L, according to the days of modeling and different dosages of FTSJRF. D1, D3, D10, D10H, D10M and D10L group mice were intratracheally administered with 15 µg SARS-CoV-2 spike protein; mice in the D10H, D10M, and D10L groups were intragastrically administered FTSJRF (46, 23 and 11.5 g/kg, respectively). Observe the pathological changes in lung tissues, expression of inflammatory factors, and mucins in different groups of mice using HE and PAS staining methods, as well as ELISA and RT-qPCR. Flow cytometry was used to detect T helper 17 (Th17)/regulatory T (Treg) cells and T helper 1(Th1)/T helper 2 (Th2) lymphocyte ratios and the proportions of conventional myeloid dendritic cells (cDCs), plasma cell-like DCs, CD80 and CD86 cells in mouse spleens.
HE and PAS staining showed that, compared to that in the normal group, the lung tissue of the D1 group mice showed a significant inflammatory damage response, whereas the D3 and D10 groups showed a gradual recovery trend. Groups D1 and D3 showed mild mucus secretion, whereas the D10 group had excessive mucus secretion. The D10 group of mice displayed increased levels of IL-4, TNF-α, IL-33 and mucin genes such as MUC1, MUC4, etc, and FTSJRF inhibited the expression of these molecules, mucus secretion and lung damage in SARS-CoV-2 spike protein-induced mouse model. Flow cytometry results showed a decrease in the number of cDCs and an abnormal recovery of DC mature cells in the D10 group. FTSJRF increased the number of cDCs and promoted DC maturation. A higher Th17/Treg ratio was observed in the D3 and D10 groups than in the normal group, whereas this ratio decreases under the effect of FTSJRF. D10 had significantly lower Th1/Th2 ratio than normal, D1 and D3 groups, and high doses of FTSJRF increased it.
FTSJRF mitigates airway inflammation and mucus secretion induced by SARS-CoV-2 spike protein. Additionally, FTSJRF regulates immune functions by promoting DC maturation and Th17/Treg and Th1/Th2 cell homeostasis.
在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白诱导的小鼠模型中，评估扶土生金康复方（FTSJRF）对气道炎症、黏液分泌和免疫反应的影响。
根据建模天数和FTSJRF不同剂量，将42只小鼠随机分为七组：正常组、D1组、D3组、D10组、D10H组、D10M组和D10L组。D1组、D3组、D10组、D10H组、D10M组和D10L组小鼠经气管内给予15 μg SARS-CoV-2刺突蛋白；D10H组、D10M组和D10L组小鼠分别经胃内给予FTSJRF（46、23和11.5 g/kg）。采用苏木精-伊红（HE）和过碘酸-雪夫（PAS）染色法、酶联免疫吸附测定（ELISA）和逆转录-定量聚合酶链反应（RT-qPCR）观察不同组小鼠肺组织的病理变化以及炎症因子和黏蛋白的表达。采用流式细胞术检测小鼠脾脏中辅助性T细胞17（Th17）/调节性T（Treg）细胞、辅助性T细胞1（Th1）/辅助性T细胞2（Th2）淋巴细胞比例以及传统髓样树突状细胞（cDCs）、浆细胞样树突状细胞、CD80和CD86细胞的比例。
HE和PAS染色显示，与正常组相比，D1组小鼠肺组织呈现明显的炎症损伤反应，而D3组和D10组呈现逐渐恢复趋势。D1组和D3组有轻度黏液分泌，而D10组有过多黏液分泌。D．10组小鼠白细胞介素-4（IL-4）、肿瘤坏死因子-α（TNF-α）、白细胞介素-33以及黏蛋白1（MUC1）、黏蛋白4（MUC4）等黏蛋白基因水平升高，而FTSJRF在SARS-CoV-2刺突蛋白诱导的小鼠模型中抑制了这些分子的表达、黏液分泌和肺损伤。流式细胞术结果显示，D10组cDCs数量减少，树突状细胞成熟细胞异常恢复。FTSJRF增加了cDCs数量并促进了树突状细胞成熟。D3组和D10组的Th17/Treg比值高于正常组，而在FTSJRF作用下该比值降低。D10组的Th1/Th2比值显著低于正常组、D1组和D3组，高剂量FTSJRF使其升高。
FTSJRF减轻了SARS-CoV-2刺突蛋白诱导的气道炎症和黏液分泌。此外，FTSJRF通过促进树突状细胞成熟以及Th17/Treg和Th1/Th2细胞稳态来调节免疫功能。
