Ginkgo biloba extract (GBE) has been found to be effective in inhibiting the airway and systemic inflammatory response and improve airway remodeling in rat models of chronic obstructive pulmonary disease (COPD) , but the mechanism remains unclear.

To discuss the mechanism of GBE regulating alveolar macrophage autophagy through phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) /mammalian target of rapamycin (mTOR) signaling pathways to prevent and treat COPD.

A total of 90 SPF male Wistar rats were equally randomized into normal control group, COPD model group, GBE group, bicalutamide group, rapamycin group, and Taselisib group. The normal control group were normally fed except that normal saline was injected into their trachea on the 1st and 14th days of intervention, the other 5 groups were treated with exposure to cigarette smoking combined with intratracheal injection of lipopolysaccharide (LPS) to establish rat models of COPD. The GBE group received intraperitoneal injection of Shuxuening injection from the 15th day to the 28th day of the experiment, while bicalutamide, rapamycin, and Taselisib groups were given bicalutamide, rapamycin, and taselisib, respectively, from the 29th day to the 42nd day of the experiment. HE staining was used to observe alveolar pathological changes and airway remodeling. ELISA was used to detect the levels of interleukin -6 (IL-6) and interleukin -8 (IL-8) in alveolar lavage fluid (BALF) and the serum. The number of alveolar macrophages was counted under microscope. The ultrastructure of alveolar macrophages was observed by transmission electron microscope. Western blotting was used to measure the expression levels of autophagy-related proteins in alveolar macrophages. The ratio of microtubule-associated protein light chain 3 (LC3) -Ⅱ/LC3-Ⅰwas calculated subsequently.

As of the models being successfully established, the rats in normal control, COPD model, GBE, bicalutamide, rapamycin, and Taselisib groups numbered 12, 11, 12, 12, 12, and 11, respectively. H&E staining showed that the degree of alveolar injury in COPD model group was more severe than that of GBE, bicalutamide, rapamycin, or Taselisib group (P<0.05) . COPD model group had larger mean linear intercept and mean alveolar area as well as less mean alveolar number than GBE, bicalutamide, rapamycin, or Taselisib group (P<0.05) . Moreover, COPD model group had less complete bronchial wall structure than GBE, bicalutamide, rapamycin, or Taselisib group. The levels of BALF and serum IL-6 and IL-8 in COPD model group were higher than those of each of other five groups (P<0.05) . Among all groups, the number of macrophages in the normal control group was the lowest, while that of COPD model group was the highest (P<0.05) .Transmission electron microscopy showed that COPD model group had less autophagolysosomes in alveolar macrophages than GBE, bicalutamide, rapamycin, or Taselisib group. The normal control group had higher expression levels of PI3Kp110α, Akt, p-Ak, mTOR and p-mTOR and lower ratio of LC3-II/LC3-I than each of other five groups (P<0.05) . COPD model group had higher expression levels of PI3Kp110α, Akt, p-Akt, mTOR and p-mTOR, and lower ratio of LC3-Ⅱ/LC3-Ⅰ compared with GBE, bicalutamide, rapamycin or Taselisib group (P<0.05) .

GBE maintained the autophagy function of alveolar macrophages, reduced macrophage infiltration, inhibited the inflammatory response and alveolar damage, and improved airway remodeling in model rats of COPD through regulating the PI3K/Akt/mTOR signaling pathway.