ABSTRACT
Objective:To explore the effect of hypoxia-inducible factor （HIF）-1<italic>α</italic> on T helper 17 （Th17）/regulatory T cell （Treg） balance in ulcerative colitis and the intervention mechanism of Shaoyaotang. Method:Forty-eight SD rats were randomly divided into normal group （normal saline）， model group， mesalazine group （0.42 g·kg<sup>-1</sup>）， Shaoyaotang group （11.1 g·kg<sup>-1</sup>）， inhibitor group ［2-methoxyestradiol （2ME<sub>2</sub>）， 0.015 g·kg<sup>-1</sup>］， and Shaoyaotang+inhibitor group. The ulcerative colitis model was induced by 2，4，6-trinitrobenzene sulfonic acid （TNBS）. The rats in all groups received corresponding treatments for 7 d， and the general condition and disease activity index （DAI） were observed. Hematoxylin-eosin （HE） staining was used to observe histopathological changes of the colon. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum levels of interleukin （IL）-10， IL-17， and IL-23 in rats. Western blot was used to detect the expression levels of forkhead box protein 3 （FoxP3）， retinoic acid-related orphan receptor <italic>γ</italic>t （ROR<italic>γ</italic>t）， and HIF-1<italic>α</italic> proteins in the colon tissue. Result:Compared with the normal group， the model group showed elevated disease activity index （DAI） score and pathological score for intestinal mucosa （<italic>P</italic><0.01）， reduced serum IL-10 level （<italic>P</italic><0.01）， up-regulated IL-17 and IL-23 levels （<italic>P</italic><0.01）， increased ROR<italic>γ</italic>t and HIF-1<italic>α</italic> expression （<italic>P</italic><0.01）， and decreased FoxP3 protein expression （<italic>P</italic><0.01）. Compared with the model group， the Shaoyaotang group displayed diminished DAI score and pathological score for intestinal mucosa （<italic>P</italic><0.05， <italic>P</italic><0.01）， increased serum IL-10 level （<italic>P</italic><0.01）， decreased IL-17 and IL-23 levels （<italic>P</italic><0.01）， dwindled protein levels of ROR<italic>γ</italic>t and HIF-1<italic>α </italic>（<italic>P</italic><0.01）， and up-regulated expression of FoxP3 （<italic>P</italic><0.01）. Compared with the inhibitor group， the Shaoyaotang group and the Shaoyaotang+inhibitor group exhibited significant differences in the expression of ROR<italic>γ</italic>t， FoxP3， and HIF-1<italic>α</italic> proteins （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Shaoyaotang could effectively treat ulcerative colitis， and the underlying mechanism of action might be related to the regulation of Th17/Treg rebalance by inhibiting HIF-1<italic>α</italic>.
ABSTRACT
Objective: To investigate effect of Shaoyaotang on intestinal mucosal immune barrier induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats with ulcerative colitis.Method: Sixty SD rats were randomly divided into normal group,model group,mesalazine group (0.067 mg·kg-1),low,medium and high-dose Shaoyaotang groups (1.8,3.6,7.2 g·kg-1).In the TNBS-induced ulcerative colitis model,saline,mesalazine,peony soup were administered by gavage for 7 days.Hematoxylin-eosin (HE) staining was used to detect the histopathological changes of colon tissue.The number of CD4+T lymphocytes and the expression of secretory immunoglobulin A (SIgA) in intestinal mucosa were detected by immunohistochemistry and Western blot.Result: Compared with normal group,the scores of intestinal mucosal injury and the pathological scores in model group increased significantly (P+T lymphocytes and SIgA in the intestinal mucosa of model group decreased significantly (PP+T lymphocytes and SIgA in the intestinal mucosa of rats in each group elevated significantly (PPP+T lymphocytes and SIgA protein in the intestinal mucosa of rats in middle and high doses Shaoyaotang groups increased significantly (PConclusion: Shaoyaotang can reduce the intestinal mucosal damage and protect the intestinal mucosal immune barrier by increasing the number of CD4+T cells and the expression of SIgA secretion in the intestinal mucosa.
ABSTRACT
Ulcerative colitis (UC) is a common chronic non-specific intestinal inflammation, which has a long course and is difficult to cure, and the incidence is increasing year by year. Helper T cells 17 (Th17) are one of immune-promoting cells, while regulatory sputum cells (Treg) are immunosuppressive cells, and Th17 cells and regulatory T cells together maintain the balance of the body's immune microenvironment. During progression of UC, the population of sputum helper cells 17 (Th17 cells) that cause inflammation generally increases, while the number of sputum regulatory T cells that inhibit Th17 cell activity decreases. Among them, Th17 cells mediate immune response, regulatory T cell-mediated immunosuppression, and the balance between the two plays a key role in the inflammation and immune process of ulcerative colitis. Although Western medicine treatment of UC has certain effects, however, The frequency and severity of side effects, inconvenient dose adjustments, and partial price excessions limit their clinical application.As a traditional medicine in China, traditional Chinese medicine(TCM) has multi-target, multi-link and multi-channel treatment characteristics, and has unique advantages and broad prospects in anti-ulcerative colitis. In recent years, the TCM field has taken Th17/Treg balance as the entry point, and carried out a large number of clinical and experimental studies on the intervention of TCM in Th17/Treg balance in UC, and achieved certain results. Clinical and experimental evidence clearly indicates intervention in Th17/Treg. It is an important mechanism of action of TCM in the treatment of ulcerative colitis. This paper mainly summarizes and analyzes the intervention effects of TCM monomer, component or active ingredient and TCM compound on Th17/Treg balance in UC, which is helpful for people to understand Chinese medicine intervention in UC more accurately and comprehensively. The mechanism of action of Th17/Treg balance provides a reference for the clinical design of a treatment plan for anti-ulcerative colitis.
ABSTRACT
Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×10/L. CD4+T cells in two patients were less than 200×10/L. Four patients had elevated serum cytomegalovirus DNA. The level of β-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.