Abstract: Objective To investigate the molecular mechanism of polysaccharides from Atractylodes macrocephala koidz.(PAM) to treat severe pneumonia. Methods Sixty male SD rats were randomly divided into control group, model group (inoculation of Klebsiella pneumonia by tracheal puncture), positive control group (levofloxacin, 18 mg/kg), PAM low-dose group (50 mg/kg) and PAM high-dose group (200 mg/kg) with 12 in each. After occurrence of severe pneumonia, the rats were orally administered the medicine once daily for 7 day. The lung tissue underwent histopathological examination using HE staining microscopy to find the pathological alterations and evaluate the extent of injury. Wet/dry ratio of lung tissue was measured by weighing method. The leukocytes and neutrophils counts in peripheral blood were determined by hematology analyzer. The level of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and IL-6 in serum and bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay. The expression of proteins related to the Toll-like receptor 4 (TLR4) / myeloid differentiation factor 88 (MyD88)/nuclear factor-κB(NF-κB) signaling pathway in lung tissues was detected using Western blot analysis. Results Compared with the control group, lung injury score and wet/dry ratio, the number of leukocytes and neutrophils in peripheral blood, the level of TNF-α, IL-1β and IL-6 in serum and in BALF,protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissues from model group were all significantly increased(P＜0.05). The lung injury of rats in each levofloxacin treatment group exhibited significant improvement compared to the model group. Among them, the number of leukocytes and neutrophils in peripheral blood of rats in PAM high-dose group decreased significantly(P＜0.05); The level of TNF-α, IL-1β and IL-6 in serum and BALF, the protein expression of TLR4 and MyD88 and the phosphorylation level of NF-κB p56 in lung tissue were significantly decreased(P＜0.05). Conclusions The administration of PAM exerts a specific protective effect against Klebsiella pneumoniae-induced pneumonia in rats, potentially suppress inflammatory response through modulation of the TLR4/MyD88/NF-κB signaling pathway.

Key words: polysaccharides from Atractylododes macrocephala koidz., severe pneumonia, inflammation, TLR4/MyD88/NF-κB