الملخص
ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4+ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.
الملخص
Objective:To explore the potential mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis through network pharmacology and experimental verification.Methods:The active components and targets of Tianshui Dichang Decoction were screened by TCMSP. The related targets of ulcerative colitis were screened by OMIM, GeneCard and TTD databases, and the effective component targets of Tianshui Dichang Decoction were intersected with the potential targets of ulcerative colitis. The PPI network was constructed by STRING database to screen the core targets, and the "Chinese materia medica-disease-active components-target" network was constructed by Cytoscape 3.8.0 software. GO function and KEGG pathway enrichment analysis were carried out using Metascape database. 48 mice were divided into control group, model group, mesalazine group (0.3 g/kg) and Tianshui Dichang Decoction low-, medium-, and high-dosage groups (7.5,15 and 30 g/kg) according to random number table method, with 8 mice in each group. Except the control group, the ulcerative colitis model was established in other groups. After 7 days of intervention with corresponding drugs, the disease activity index (DAI) was scored, the pathological changes of colon were observed by HE staining, and the expressions of IL-6, STAT3mRNA and protein in colon tissue were detected by PCR and Western blot methods.Results:Totally 127 active components in Tianshui Dichang Decoction and 560 targets of ulcerative colitis were obtained. 89 intersecting targets of Tianshui Dichang Decoction and ulcerative colitis were obtained, and the core targets included IL6, TNF, IL1B, AKT1, TP53, VEGFA, JUN, PTGS2, CXCL8, CCL2, STAT3, MMP9 and so on. Oxidative stress response, lipopolysaccharide metabolism, bacterial response, signal transduction and other biological processes were mainly involved, mainly through the cancer pathway, IL17, TNF, MAPK and other signal pathways to play a role in the treatment of ulcerative colitis. The results of experimental verification showed that the DAI score, the expressions of IL-6 and STAT3 protein in colon tissue of Tianshui Dichang Decoction medium- and high-dosage groups.decreased ( P<0.05). The levels of IL-6 and STAT3 mRNA in colon tissue decreased in the Tianshui Dichang Decoction low-, medium- and high-dosage groups.groups ( P<0.05). Conclusion:Tianshui Dichang Decoction has a certain therapeutic effect on UC through component-multitarget-signal pathway, and its mechanism is related to regulating IL-6/STAT3 signal pathway and inhibiting intestinal mucosal inflammation.
الملخص
Objective To evaluate the changes of left ventricular hemodynamics and systolic function in patients with apical aneurysm after percutaneous ventricular restoration ( PVR) by echocardiography . Methods Fifty patients with apical aneurysm were divided into PVR group ( 25 cases) and conservative treatment group ( control group ,25 cases ) . Two-dimensional transthoracic echocardiography ( 2D-TTE ) combined with real-time three-dimensional transesophageal echocardiography( RT-3DTEE) were applied for all the subjects in PVR group on preoperative ,one week after operaction ,three months after operaction and in control group on initial stage of prevent ventricular remodeling therapy ,one week after therapy ,three months after therapy to obtain left ventricular end-diastolic diameter( LVEDD) ,left ventricular end-systolic diameter( LVSDD) ,left ventricular end-diastolic volume( EDV ) ,end-systolic volume( ESV ) ,left ventricular ejection fraction( LVEF) ,left ventricular fractional shortening ( LVFS ) ,body surface area ( BSA ) ,stroke volume( SV) ,stroke volume index ( SVI) ,cardiac output ( CO ) ,cardiac output index ( CI) . Results There were significant differences in all parameters( P < 0 .05) especially in LVEF and SVI( P < 0 .01) between PVR group and control group in the following three months after operaction ,while there was no significant difference of the following one week after operaction( P > 0 .05) .Compared with preoperative ,there was no difference in all parameters in the following one week after operaction ( P > 0 .05) ,there was significant increase in SV and significant reduce in LVEDD and EDV ( P < 0 .01) between preoperative and in the following three months after operaction ,while there was no significant difference between preoperative and in the following one week after operaction ( P > 0 .05 ) .For the control group there was no significant difference between initial stage of prevevt ventricular remodeling therapy and in the following one week or three months after operaction .Conclusions PVR has a definite effect on left ventricular hemodynamics and systolic function in patients with apical aneurysm in the short term ,while 2D-TTE and RT-3DTEE provides a reliable basis for clinical to evaluate the effect of the PVR .