The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells.

OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

[Effects of simvastatin on pulmonary fibrosis and endothelial - mesenchymal transition in the pulmonary fibrosis tissue of rats].

Objective: To investigate the effects of simvastatin (SIM) on pulmonary fibrosis and the expression of VE-cadherin(VE-cad),vimentin(VIM) and alpha-smooth muscle actin(α-SMA)in the pulmonary fibrosis tissue of rats. Methods: Sixty healthy male SD rats were randomly divided into control group(group A), bleomycin group(group B), 5 mg SIM group (group C) and 10 mg SIM group (group D),15 rats in each group. The model of rat pulmonary fibrosis was established by itraperitoneal injection of bleomycin(5 mg/kg). Since the first day of modeling, the rats of group C and D were treated with simvastatin suspension 5 mg/(kg·d) and 10 mg/(kg·d) by intragastric administration everyday, and the rats of group A and B were treated with equal volume of saline 10 ml/(kg·d) everyday. Five rats of each group were sacrificed randomly at the 7th, 14th and 28th day. Masson staining was used to observe the morphological changes of lung tissue in rats. The degree of fibrosis in lung tissues of each group was evaluated by the content of hydroxyproline (HYP) . The microvessel density (MVD) was analyzed by immunohistochemistry,The expressions of protein and mRNA of VE-cad, VIM and α-SMA were determined by immunohistochemistry and RT-PCR. Results: ①Compared with group A, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in lung tissues of groups B, C and D were increased significantly at the 7th, 14th and 28th day(all P＜0.05), which reached highest level at the 28th day. However, the mRNA and protein expression levels of VE-CAD were decreased significantly at the corresponding time (P＜0.05), which reached lowest level at 28th day. ②Compared with group B, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in groups C and D were decreased at the 7th, 14th and 28th day (all P＜0.05), which were decreased more obviously in group D at the 28th day. However, the mRNA and protein expression levels of VE-CAD were increased at the corresponding time (all P＜0.05), which were increased more obviously in group D at the 28th day. Conclusion: Simvastatin can reduce the degree of pulmonary fibrosis in rats through inhibiting the process of EnMT, which can enhance the expression of VE-cad and reduce the expression of VIM and α-SMA.

[The expression of 5-HTR2B、E-cad、α-SMA in the pulmonary fibrosis in rats].

OBJECTIVE: To observe the expression of 5-Hydroxytryptamine 2B receptor (5-HTR2B)、E-cadherin (E-cad)、alpha-smooth muscle actin(α-SMA) in the bleomycin -induced pulmonary fibrosis tissue of rats. METHODS: Forty-five healthy male SD rats were randomly di-vided into control group,bleomycin group and bleomycin+prednisone group(n=15). Five rats in each group randomly sacrificed at the 7th、the 14th and the 28th day after eastablishing models. The lung tissue was observed by microscope in HE and Masson staining. Lung hydroxypro-line (HYP) content was evaluated. The expression of protein and mRNA of 5-HTR2B, E-cad and α-SMA were analyzed by immunohistoche-mistry and/or RT-PCR. RESULTS: A dynamic changes from alveolitis to pulmonary fibrosis could be observed in the slices by HE and Masson staining. The experimental results by immunohistochemistry and RT-PCR showed that the protein and mRNA expression of 5-HTR2B and a-SMA enhanced rat pulmonary fibrosis (P<0.05) and reached the highest at the 28th day; the corresponding protein and mRNA expression of E-cad reduced (P<0.05), and reduced to the lowest value at the 28th day. Compared with bleomycin group, the corresponding mRNA and protein expression of 5-HTR2B and a-SMA in bleomycin+prednisone group had decreased (P<0.05); however, the corresponding mRNA and protein expression of E-cad had increased(P<0.05). CONCLUSIONS: 5-HTR2B is involved in the pathogenesis of pulmonary fibrosis throught epithelial-mesenchymal transition (EMT).