中药方剂葛根芩连汤缓解LPS诱导小鼠回肠炎症作用研究

本文拟研究葛根芩连汤(GQD)对脂多糖(LPS)刺激诱导的小鼠回肠炎症的抑制作用与对肠道菌群的调节作用。雄性C57BL/6小鼠经口给予治疗剂量的GQD和抗生素(ABX) 7 d,第8天腹腔注射10 mg/kg的LPS。使用HE染色和AB-PAS染色进行回肠组织学评价;RT-qPCR检测回肠组织炎症因子(IL-1 β、IL-6、TNF-α、IL-10、IL-17和IL-22)、LPS受体(CD14、TLR4和MyD88) mRNA水平;ELISA测定超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;对盲肠内容物与粪便进行细菌革兰氏染色计数。GQD显著降低了小鼠回肠组织中由LPS诱导的炎症因子的mRNA水平(IL-1 β、IL-6、TNF-α、IL-17、IL-22、IL-10),LPS受体(CD14、MyD88、TLR4)的表达、SOD活性、MDA含量、修复了上皮细胞之间的紧密连接。GQD一定程度上改变了肠道菌群的结构。GQD预处理可以通过改变肠道菌群和肠屏障在一定程度上减轻LPS导致的肠损伤。This paper investigates the inhibitory effects of Ge Gen Qin Lian Decoction (GQD) on LPS-induced intestinal inflammation and dysbiosis. Male C57BL/6 mice were given therapeutic doses of GQD and antibiotics (ABX) orally for 7 days, followed by LPS challenge (10 mg/kg) intraperitoneally on day 8. Histological evaluation was performed using HE and AB-PAS staining;RT-qPCR was performed to detect inflammatory factors (IL-1β, IL-6, TNF-α, IL-10, IL-17 and IL-22), LPS receptors (CD14, TLR4 and MyD88) at mRNA levels;Superoxide Dismutase (SOD) activity and Malonic dialdehyde (MDA) content were determined using ELISA;Cecum and fecal bacterial Gram staining and 16S rDNA-Seq were used to analyze the changes of intestinal flora. GQD significantly reduced LPS-induced inflammatory factors (IL-1β, IL-6, TNF-α, IL-17, IL-22, and IL-10), expression of LPS receptors (CD14, TLR4) and MyD88. GQD decreased SOD activity and MDA content, and repaired tight junctions between epithelial cells in mouse ileal tissues. GQD somewhat altered the structure. Pretreatment with GQD can change the intestinal flora and the intestinal barrier, and reduce the intestinal injury caused by LPS.

Effect of infliximab on small bowel stenoses in patients with Crohn's disease

AIM: To assess prospectively small bowel stenoses in Crohn's disease (CD) patients treated with infliximab using Small Intestine Contrast Ultrasonography (SICUS). METHODS: Twenty patients (M 12, age, 42.7 ± 11.8 years), 15 of whom showed obstructive symptoms indicating the presence of small bowel stenosis, and 5 without stenosis, were treated with infliximab (5 mg/kg at wk 0, 2, 6 and 5 mg/kg every 8 wk thereafter) for steroid refractoriness, fistulizing disease, or to avoid high-risk surgery. SICUS was performed at the induction phase and at regular time intervals during the follow-up period of 34.7 ± 16.1 mo (range 7-58). Small bowel stenoses were detected by SICUS, endoscopy and MRI. RESULTS: In no case was progression of stenoses or the appearance of new ones seen. Of the 15 patients with stenosis, 5 stopped treatment after the induction phase (2 for no response, 3 for drug intolerance, one of whom showed complete regression of one stenosis). Among the remaining 10 patients, a complete regression of 8 stenoses (1 stenosis in 5 patients and 3 stenoses in one patient) was observed after 6-22 infliximab infusions. CONCLUSION: In patients with CD treated with infliximab we observed: (a) No progression of small bowel stenosis and no appearance of new ones, (b) Complete regression of 1/22 stenosis after the induction phase and of 8/15 (53.3%) stenosis after 6-22 infusionsduring maintenance therapy.

Pregnancy related issues in inflammatory bowel disease: Evidence base and patients' perspective

Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. Women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. When indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. Women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery. While the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.

Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn's disease of the terminal ileum

Although the association between inflammatory bowel disease and gastrointestinal infections has been suggested, the mechanisms involved in the pathogenesis of Crohn＇s disease （CD） are still undetermined. We report the case of a man, who presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis infection, who was later diagnosed with Crohn＇s disease. This case is in keeping with recent evidence in the literature which suggests that CD is a disease linked to abnormal immune responses to enteric bacteria in genetically susceptible individuals.

Enteropathic spondyloarthropathy:A common genetic background with inflammatory bowel disease?

The association between spondyloarthropathy and in flammatory bowel disease(IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies.Most studies indicate that as many as 10%15% of cases of IBD are complicated by ankylosing spondylitis(AS) or other forms of spondylarthritis(SpA).Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronic ity of articular complications.Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonos copy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time.The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among f irstand seconddegree relatives of affected AS or IBD patients and f inally, the increased crossrisk ratios between AS and IBD, strongly suggest a shared genetic background.So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS.Although functional studies are still needed to better understand its pathogenic role, great ef fort is being spent therapeutically targeting this pathway that may prove effective for both disorders.