关键词: 麻杏苦甘汤, 油酸, SD大鼠, 急性肺损伤, 肺水肿, 纤维化, 巨噬细胞极化

Abstract: BACKGROUND: Maxing Kugan Decoction is a Chinese medicinal preparation derived from "San Ao Tang," which is effective in relieving cough and asthma, clearing internal heat, nourishing yin and moistening dryness. It has been widely used in the treatment of respiratory tract infectious diseases in Ningxia and neighboring areas, and can effectively prevent and control the occurrence and development of acute lung injury. However, its mechanism of action is still unclear in the treatment of acute lung injury.
OBJECTIVE: To explore the dynamic preventive and therapeutic effects of Maxing Kugan Decoction on oleic acid-induced acute lung injury in Sprague-Dawley rats. 
METHODS: Forty-five Sprague-Dawley rats were allocated into three groups: control (5 rats), model (20 rats), and Maxing Kugan Decoction (20 rats). The Maxing Kugan Decoction group received daily gavage for 7 days prior to modeling. At 1 hour after final administration, both the model and Maxing Kugan Decoction groups were injected with oleic acid via the tail vein to induce the acute lung injury model. Five rats from each group were sampled at 3, 6, 12, and 24 hours after injection to evaluate lung tissue function through blood gas analysis. Lung tissue edema and damage to the alveolar-capillary barrier were evaluated through the measurement of the lung coefficient, lung wet-to-dry weight ratio, total cell count in bronchoalveolar lavage fluid, total protein concentration, and lung permeability index. The inflammatory response in lung tissue was assessed by quantifying the levels of inflammatory factors and detecting the number and polarization of macrophages using immunofluorescence. The extent of lung tissue injury was determined using hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The progression of pulmonary fibrosis following lung injury was examined using Masson staining.
RESULTS AND CONCLUSION: (1) Compared with the control group, the rats in the model group exhibited pronounced symptoms of shortness of breath, reduced activity, and cyanosis of the lips and face immediately following the tail vein injection of oleic acid. After 3 hours, there was a notable decrease in the partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), the partial pressure of carbon dioxide (PaCO2), lung coefficient, and lung wet-to-dry weight ratio. Additionally, the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in bronchoalveolar lavage fluid were significantly elevated, accompanied by an increase in the total cell count and lung permeability index. Histopathological analysis revealed significant inflammatory infiltration, tissue edema, thickening of the alveolar septa, apoptosis of pulmonary cells, and mild collagen fiber hyperplasia and deposition. Additionally, there was a notable polarization of rat lung macrophages towards the M1 phenotype. At 6 hours, all injuries were further exacerbated, and blood gas indices declined to their lowest levels. By 12 hours, although blood gas indices showed recovery, histopathological staining of lung tissues indicated compensatory alveolar enlargement or shrinkage. Concurrently, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid reached the peak. At 24 hours, there was an alleviation in the blood gas indices and inflammatory response, but the oxygenation index remained within the range indicative of acute lung injury. Furthermore, lung tissue damage and edema continued to worsen, accompanied by significant collagen fiber hyperplasia and deposition. (2) Compared with the model group during the same period, Maxing Kugan Decoction demonstrated a significant capacity to mitigate the aforementioned pathological alterations, delay the onset of acute lung injury, inhibit the polarization of macrophage, and reduce inflammatory responses, tissue edema, collagen fiber deposition, and apoptosis in lung tissue cells. To conclude, Maxing Kugan Decoction effectively prevents the occurrence of oleic acid-induced acute lung injury, diminishes the severity and duration of acute lung injury, and promotes the recovery from tissue edema and collagen fiber deposition following acute lung injury.

Key words: Maxing Kugan Decoction, oleic acid, Sprague-Dawley rats, acute lung injury, pulmonary edema, fibrosis, polarization of macrophage