鸢芩胶囊对脂多糖诱导小鼠急性肺损伤的作用及肠道菌群的影响OA

Objective:To explore the mechanism of action of Yuanqin(鸢芩)Capsules on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice and its effect on the gut microbiota.Methods:Thirty-six male C57BL/6J mice were randomly divided into normal control group,model control group,prednisone acetate 50 mg/kg group,and Yuanqin Capsules 1.95,3.90,and 7.80 g/kg groups.The ALImodel was established by intratracheal instillation of LPS.The total cell count and white blood cell count in bronchoalveolar lavage fluid(BALF)were measured.Hematoxylin and eosin(HE)staining was used to observe the histopathological changes in lung tissue.Enzyme-linked immunosorbent as-say(ELISA)was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in lung tissue.Western blot was used to detect the protein expression levels of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and their phosphorylated forms(p-PI3K,p-AKT),IL-6,TNF-α,inducible nitric oxide synthase(iNOS),man-nose receptor type C-1(MRC1)and arginase-1(Arg1)in lung tissue.16S rRNA gene sequencing was used to detect the composition and diversity of the gut microbiota in fecal samples.Results:Compared with the normal control group,the model control group exhibited significantly increased inflammatory cell count in BALF,lung injury score,and IL-6 and TNF-α levels(P<0.01).The ratios of p-PI3K/PI3K and p-AKT/AKT,as well as the expressions of Arg1 and MRC1,significantly decreased(P<0.05 or P<0.01),while the protein expressions of iNOS,IL-1β and TNF-α were significantly upregulated(P<0.05 or P<0.01).Compared with the model control group,the total cell count and the white blood cell count in BALF significantly decreased in the Yuanqin Capsules 1.95 g/kg group(P<0.01).The lung injury scores sig-nificantly decreased in the Yuanqin Capsules 1.95 g/kg and 7.80 g/kg groups(P<0.01).The IL-6 levels in lung tis-sue were reduced in all dosage groups(P<0.05 or P<0.01).TNF-α levels significantly decreased in the Yuanqin Cap-sules 3.90 g/kg and 7.80 g/kg groups(P<0.01).In the Yuanqin Capsules 7.80 g/kg group,the protein expression levels of Arg1,MRC1,and the ratios of p-AKT/AKT and p-PI3K/PI3K were upregulated(P<0.05 or P<0.01),while the protein expression levels of TNF-α,iNOS and IL-1β were downregulated(P<0.05 or P<0.01).Gut microbiota a-nalysis showed that the Yuanqin Capsules 7.80 g/kg group significantly remodeled the gut microbiota structure in ALI mice,reduced microbiota diversity,decreased pro-inflammatory genera such as Desulfovibrio and Mucispirillum,and en-riched beneficial bacteria such as Akkermansia.It was also suggested that microbial functions related to inflammation and metabolic pathways might be modulated.Conclusion:Yuanqin Capsules may exert a protective effect against ALI by ac-tivating the PI3K/AKT signaling pathway,downregulating the expression of pro-inflammatory factors,upregulating the an-ti-inflammatory proteins Arg1 and MRC1 in lung tissue,and modulating the structure of the gut microbiota.