ABSTRACT
Objective To investigate the therapeutic effect of Yudantong decoction in mice with α-naphthyl isothiocyanate (ANIT)-induced cholestasis, as well as its targets and mechanism based on intestinal flora and intestinal barrier function. Methods A total of 24 C57BL/6 mice were randomly divided into control group, model group, Yudantong decoction group (YDTF group), and ursodeoxycholic acid (UDCA) group, with 6 mice in each group. The mice in the model group, the YDTF group, and the UDCA group were given ANIT 35 mg/kg/day by gavage on days 1, 4, 7, 10, and 13, and those in the YDTF group and the UDCA group were given Yudantong decoction or UDCA by gavage for 15 consecutive days; related samples were collected on day 16. Liver histopathology was observed, and liver function parameters were measured; immunohistochemistry was used to measure the protein expression levels of caspase-1, interleukin-1β (IL-1β), and FXR in the liver, and flow cytometry was used to measure the percentages of CD11b + , CD86 + , and CD45 + immune cells in the liver; 16S rDNA sequencing and information analysis were performed for fecal microorganisms; immunohistochemistry was used to measure the protein expression of the intestinal FXR/NLRP3 pathway, and immunofluorescence assay was used to measure the protein expression of intestinal E-cadherin and occludin. A one-way analysis of variance was used for comparison of continuous data with homogeneity of variance between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Welch test was used for comparison of data with heterogeneity of variance between multiple groups, and the Games-Howell test was used for further comparison between two groups. Results HE staining showed that the model group had partial hepatocyte fatty degeneration, massive necrosis of hepatocytes in hepatic lobules, damage of lobular structure, and massive inflammatory cell infiltration, and the YDTF group and the UDCA group had alleviation of hepatocyte fatty degeneration and hepatocyte necrosis in hepatic lobules, with a reduction in inflammatory cells. Compared with the control group, the model group had significantly higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and total bile acid (TBA) (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the serum levels of ALT, AST, GGT, ALP, TBil, DBil, and TBA (all P < 0.05), and the UDCA group had significant reductions in the serum levels of GGT, TBil, DBil, and TBA (all P < 0.05). Compared with the control group, the model group had significant increases in the levels of caspase-1 and IL-1β and a significant reduction in the expression of FXR in the liver (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the levels of caspase-1 and IL-1β in the liver and the UDCA group had a significant reduction in the level of IL-1β in the liver, and both the YDTF group and the UDCA group had a significant increase in the expression level of FXR in the liver (all P < 0.05). The model group had a significant change in the composition of intestinal flora compared with the control group ( P < 0.05); there was a significant difference in the structure of intestinal flora between the YDTF group and the model group ( P < 0.05), and there was also a significant difference in the composition of intestinal flora between the UDCA group and the control/model groups ( P < 0.05). Compared with the control group, the model group had a significant increase in the abundance of intestinal Akkermansia muciniphila and a significant reduction in the abundance of Lactobacillus johnsonii (both P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant reduction in the abundance of intestinal Akkermansia muciniphila , and the YDTF group had a significant increase in the abundance of Lactobacillus murinus , while the UDCA group had significant increases in the abundance of Lactobacillus murinus and Bifidobacterium pseudolongum (all P < 0.05). Compared with the control group, the model group had a significant reduction in the protein expression of intestinal FXR, a significant increase in the protein expression of intestinal NLRP3, and significant reductions in the expression of intestinal E-cadherin and occludin (all P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant increase in the protein expression of intestinal FXR, a significant reduction in the protein expression of intestinal NLRP3, and significant increases in the expression of intestinal E-cadherin and occludin (all P < 0.05). Conclusion Yudantong decoction can alleviate liver injury in mice with ANIT-induced cholestasis, possibly by improving intestinal flora and enhancing intestinal barrier function.
ABSTRACT
Objective:To explore clinical manifestations, imaging features and prognosis of juvenile idiopathic arthritis (JIA) combined with lung injury, aiming to improve the understanding of the disease.Methods:Clinical data from 464 children with JIA who were hospitalized in Beijing Children′s Hospital from January 2016 to September 2019 were retrospectively analyzed.Their clinical manifestations, high resolution CT (HRCT) features, lung function and follow-up of children with lung injury were analyzed.Results:Among 464 children with JIA, 40 cases (8.62%) combined with lung injury.There were no significant differences in the age and sex between JIA children either combined with lung injury or not (all P>0.05). Among them, there were 125 cases of systemic-onset juvenile idiopathic arthritis (SoJIA) and 28 cases (22.4%) of JIA combined with lung injury, accounting for the highest proportion (70%, 28/40 cases) in JIA children combined with lung injury.Among 40 JIA children combined with lung injury, 22 cases (55.0%) had respiratory symptoms and 7 cases (17.5%) had obvious hypoxia.HRCT examination was performed in them, and the imaging findings included high-density strip or strip flocculation (75.0%, 30/40 cases), pleural thickening (45.0%, 18/40 cases), ground glass shadow (22.5%, 9/40 cases), nodular lesion (20.0%, 8/40 cases), vesicles or cystic emphysema (15.0%, 6/40 cases). Lung function was detected in 12/20 children with varying degrees of pulmonary function abnormalities, most of which were mixed ventilation dysfunction, and 2 cases still had pulmonary function abnormalities after treatment.During the follow-up for 3 months to 3.5 years, 4 cases (10%) JIA combined with lung injury died.A total of 29 children were re-examined by pulmonary CT in the follow-up visit, including 14 (48.28%) improved, 8 cases (27.58%) with no significant improvement, and 7 cases (24.14%) with repeated disease. Conclusions:JIA is a common rheumatic immune disease in children and all subtypes can be combined with lung injury, manifesting as interstitial lung disease mainly.The age and sex of JIA children combined with lung injury are not specific factors.The proportion of lung injury in SoJIA is significantly higher than that in other subtypes.SoJIA combined with macrophage activation syndrome can lead to respiratory failure, respiratory distress syndrome, and even death, which is one of the main factors leading to poor prognosis of JIA.HRCT is more sensitive to the diagnosis of lung injury.Lung function detection is a simple and easy method to evaluate and monitor lung injury.The prognosis of JIA children combined with lung injury is poor, which should be well concerned.