丽珠肠乐治疗溃疡性结肠炎的临床疗效及病理变化的研究

目的:探讨溃疡性结肠炎的微生态学改变及双歧杆菌对溃疡性结肠炎的预防和治疗作用.方法:随机选取溃疡性结肠炎的患者60人,分成二组.治疗组:口服丽珠肠乐胶囊;对照组:口服氟哌酸胶囊,柳氮磺胺吡啶栓直肠给药.疗程一个月.结果:溃疡性结肠炎的肠道内细菌数量双歧杆菌、乳杆菌显著下降(P＜0.01),肠球菌显著增加(P＜0.01).经丽珠肠乐治疗后,肠道内主要细菌的数量恢复正常,与对照组相比差异有显著性(P＜0.01);肠道黏膜病理及组织学改变基本恢复正常;临床症状改善上治疗组疗效高于对照组(P＜0.01).结论:双歧杆菌活菌制剂治疗溃疡性结肠炎效果显著,值得临床推广使用.     

纳米中药对实验大鼠脾虚型溃疡性结肠炎的治疗作用

目的 研究纳米中药对大鼠急性溃疡性结肠炎的治疗作用。方法 利用苦寒泻下中药番泻叶,灌服大鼠,使其产生脾虚症状,再用冰乙酸化学刺激法复制溃疡性结肠炎病理模型。用肉眼观察整段结肠的黏膜改变情况;梯度稀释法行粪便菌群分析,了解几种代表性的菌群的改变;一般病理切片,行染色,观察镜下病理变化。结果 与正常对照组相比,发生溃疡性结肠炎时动物的体重、肠道内优势菌群双歧杆菌（BS）和乳酸杆菌（LBS）数量均显著性降低（P〈0．05）,且伴随相关体征。结肠肉眼观察及病理切片检查恶性改变。中药通过扶植肠道优势菌群缓解了溃疡性结肠炎的症状,常态中药组与模型对照组比较差异有显著性（P〈0．05）;纳米中药小剂量即可达到满意的治疗效果,纳米中药治疗组与常态中药治疗组比较差异有显著性（P〈0．05）。结论 纳米中药可以作为一种微生态调节剂,即从调整肠道微生态失衡角度来治疗溃疡性结肠炎,具有较好的疗效。     

复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的临床研究

目的:观察复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效.方法:第一阶段将102例轻、中度溃疡性结肠炎患者随机分成A组(34例)、B组(34例)和C组(34例),分别服用美沙拉嗪片、复方嗜酸乳杆菌、美沙拉嗪+复方嗜酸乳杆菌治疗12周后观察3组临床疗效,缓解率及缓解时间.第二阶段将各组缓解者随访1年,观察3组维持时间及复发率.结果:3组临床疗效评价,临床缓解时间、缓解率比较无显著性差异见(P＞0.05),3组患者维持临床缓解时间、复发率比较差异无显著性意义(P＞0.05).所以由中国株嗜酸乳杆菌,日本株嗜酸乳杆菌、粪链球菌和枯草杆菌等四种菌粉组成的复方片剂是值得推荐的维持治疗缓解期UC的有效药物;两者联合用药并未增效,联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗是没有必要的.结论:复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效与美拉沙嗪比较无差异,没有必要联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗.     

微生态制剂治疗社区小儿腹泻217例临床观察

目的:观察微生态制剂(双歧杆菌联活菌)对社区小儿腹泻的辅助治疗。方法:217例腹泻患儿随机分为两组:治疗组116例和对照组101例。对照组给予常规治疗包括补液,纠正水、电解质紊乱及酸碱平衡,口服思密达,治疗组在常规治疗基础上加用双歧杆菌联活菌治疗。结果:治疗组总有效率94.8%,对照组总有效率76.2%,两组比较,有显著性差异(P<0.05)。结论:双歧杆菌联活菌治疗小儿腹泻疗效显著,安全,值得社区医院应用。     

复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的临床研究

目的:观察复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效。方法:第一阶段将102例轻、中度溃疡性结肠炎患者随机分成A组(34例)、B组(34例)和C组(34例),分别服用美沙拉嗪片、复方嗜酸乳杆菌、美沙拉嗪+复方嗜酸乳杆菌治疗12周后观察3组临床疗效,缓解率及缓解时间。第二阶段将各组缓解者随访1年,观察3组维持时间及复发率。结果:3组临床疗效评价,临床缓解时间、缓解率比较无显著性差异见(P>0.05),3组患者维持临床缓解时间、复发率比较差异无显著性意义(P>0.05)。所以由中国株嗜酸乳杆菌,日本株嗜酸乳杆菌、粪链球菌和枯草杆菌等四种菌粉组成的复方片剂是值得推荐的维持治疗缓解期UC的有效药物;两者联合用药并未增效,联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗是没有必要的。结论:复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效与美拉沙嗪比较无差异,没有必要联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗。     

溃疡性结肠炎患者肠黏膜菌群改变及抗体反应

目的 :探讨溃疡性结肠炎患者肠道菌群改变及机体免疫反应。方法 :采用梯度稀释法进行菌群分析 ,同时采用透射比浊法测定IgG、IgM、IgA。 结果 :发现服用培菲康的溃疡性结肠炎患者急性期菌群与正常人相比 ,肠杆菌 (8 82± 0 6 9,P <0 0 5 )、肠球菌 (7 73± 0 2 1,P <0 0 1)及小梭菌 (6 6 8± 0 78,P <0 0 1)的数量显著增加 ,而双歧杆菌 (6 89± 0 34,P <0 0 1)和乳杆菌 (6 95± 0 5 2 ,P <0 0 1)的数量明显下降 ,且缓解期与对照相比差异无显著性。拟杆菌 (7 2 6± 0 0 3,P <0 0 5 )及双歧杆菌 (7 5 9± 0 34,P <0 0 1)较急性期明显上升 ,小梭菌 (6 13± 0 6 6 ,P <0 0 1)明显下降。未服用培菲康的溃疡性结肠炎患者急性期菌群中服药前后差异无显著性。治疗前肠杆菌 (8 77± 0 89,P <0 0 1)和肠球菌 (7 75± 0 38,P <0 0 1) ,小俊菌 (6 6 4± 0 4 3,P <0 0 1)明显增加 ,而双歧杆菌 (6 98± 0 2 5 ,P <0 0 1)和乳杆菌 (6 83±0 6 2 ,P <0 0 1)明显下降。治疗后肠杆菌 (8 93± 0 6 0 ,P <0 0 1) ,肠球菌 (7 6 1± 0 39) ,小梭菌 (6 6 8±0 72 ) ,有所下降 ,双歧杆菌 (7 12± 0 35 )和乳酸杆菌 (6 6 8± 0 72 )有所上升 ,但治疗前后差异无显著性。从两组用药前后的     

双歧杆菌三联活菌片对溃疡性结肠炎患者免疫功能及Fas/FasL表达的影响

目的:研究双歧杆菌三联活菌片对溃疡性结肠炎患者免疫功能及Fas/FasL表达的影响。方法:选取2014年7月至2015年6月本院收治的84例溃疡性结肠炎患者,根据患者入院顺序分为观察组(42例)和对照组(42例)两组。对照组采取美沙拉秦肠溶片进行治疗,观察组在此基础上结合双歧杆菌三联活菌片进行治疗。分析两组患者治疗前和治疗2个月后炎症因子水平、T细胞亚群以及Fas/FasL表达情况,并比较两组患者的临床疗效。结果:观察组总的有效率显著高于对照组(P0.05)。治疗后,观察组的血清白介素-1(IL-1)、白介素-6(IL-6)、白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平显著低于对照组(P0.05),CD4+、CD4+/CD8+T细胞亚群显著高于对照组,CD8+、Fas/FasL表达显著低于对照组,差异均有统计学意义(P0.05)。结论:使用双歧杆菌三联活菌片治疗溃疡性结肠炎患者能改善患者的免疫功能及Fas/Fasl表达,减轻炎症反应,临床效果良好。     

老年性便秘肠道菌群的微生态学研究

目的 :了解老年性便秘患者肠道菌群构成特点。方法 :通过活菌定量培养计数法 ,动态观察 30例老年性便秘患者粪菌群的变化规律 ,并与 32例健康老年人比较。结果 :老年性便秘组每克粪便的活菌数(x± s)分别为 :大肠埃希菌 9.90± 1.4 9,肠球菌 7.81± 2 .6 8,乳酸杆菌 7.2 7± 1.0 1,双歧杆菌 6 .6 8± 1.2 9,类杆菌 6 .92± 0 .91,梭杆菌 10 .0 5± 1.2 1。老年健康组每克粪便各类活菌数 (x± s)分别是 :大肠埃希菌8.6 1± 2 .2 9,肠球菌 7.5 4± 2 .5 2 ,乳酸杆菌 8.2 2± 0 .6 3,双歧杆菌 9.86± 0 .4 4 ,类杆菌 9.4 1± 0 .35 ,梭杆菌7.73± 1.32。两组比较 ,老年性便秘组肠杆菌显著增高 (P<0 .0 5 ) ,梭杆菌非常显著性增高 (P<0 .0 1) ;类杆菌和双歧杆菌非常显著性减低 (均 P<0 .0 1) ;乳酸杆菌显著性减低 (P<0 .0 5 )。结论 :老年性便秘病人肠道菌群正常结构的生态平衡受到破坏 ,主要表现在以双歧杆菌为主的有益菌数量非常显著性减低 ,腐败梭菌等条件致病菌数量呈非常显著性或显著性增高。     

双歧三联活菌胶囊联合美沙拉嗪对 溃疡性结肠炎患者肠道微生态影响

目的探讨双歧三联活菌胶囊联合美沙拉嗪肠溶片对溃疡性结肠炎(ulcerative colitis,UC)患者肠道微生态的影响。方法选取2015年1月至2017年4月我院内科门诊治疗的活动期轻中度UC患者78例,随机分为观察组和对照组。两组均给予口服美沙拉嗪肠溶片1.0 g/次,4次/d。观察组在此基础上加以双歧三联活菌胶囊420 mg/次,3次/d,口服,两组均连用8周。比较两组治疗前后肠道菌群中乳杆菌、双歧杆菌、大肠埃希菌数量的变化和双歧杆菌(B)与大肠埃希菌(E)的比值变化,并评估两组治疗后临床效果。结果治疗前两组乳杆菌、双歧杆菌与大肠埃希菌及B/E比值比较,差异无统计学意义(P0.05)。治疗8周后,两组双歧杆菌、乳杆菌数量及B/E比值明显上升(P0.01),大肠埃希菌数量下降(P0.05),但观察组变化幅度更大(P0.05),且总有效率较对照组更高(χ2=4.13,P0.05)。结论双歧三联活菌胶囊联合美沙拉嗪肠溶片可治疗UC,能调节肠道菌群紊乱,重建肠道微生态平衡。     

口服双歧杆菌活菌散剂治疗急慢性腹泻的随机对照双盲双模拟多中心临床研究

目的 评价口服双歧杆菌活菌散剂治疗肠道菌群失调所致的急慢性腹泻的疗效和安全性.方法 采用阳性药物平行对照、分层区组随机、双盲双模拟、多中心临床试验设计方法.其中急性腹泻136例,慢性腹泻125例;每次口服双歧杆菌活菌散剂1包(1.0 g,含双歧杆菌活菌1.0亿个)或丽珠肠乐胶囊2粒,每日2次;急性腹泻疗程3 d,慢性腹泻疗程14 d,观察治疗后临床症状和大便常规的恢复情况,慢性腹泻中39例进行肠道菌群分析.结果 疗程结束时急性腹泻总有效率:口服双歧杆菌活菌散剂组为89.6%,丽珠肠乐胶囊组为91.2%,2组疗效相似,差异无显著性(P＞0.05);慢性腹泻总有效率:口服双歧杆菌活菌散剂组为88.1%,丽珠肠乐胶囊组为79.0%,2组疗效相似,差异无显著性(P＞0.05);慢性腹泻组中39例治疗前后进行的肠道菌群分析表明,2组双歧杆菌、拟杆菌和真杆菌治疗后比治疗前均有显著增加(P=0.00～0.02),但治疗前后增加值2组间比较差异无显著性(P＞0.05).安全性研究未发现不良反应.结论 口服双歧杆菌活菌散剂能有效治疗急慢性腹泻,疗效和安全性与丽珠肠乐胶囊相当.     

双歧杆菌对小鼠溃疡性结肠炎模型的影响

目的：研究双歧杆菌对小鼠急性溃疡性结肠炎模型的影响。方法：葡聚糖硫酸钠（DSS）制备小鼠溃疡性结肠炎模型。应用实体显微镜观察整段大肠的粘膜改变情况;普通粪便涂片观察小鼠粪便中细菌的变化,梯度稀释法行粪便菌群分析,了解几种代表性的菌群的改变;一般病理切片,行HE染色,观察镜下病理变化,结果：双歧杆菌 DSS组相比,血便不明显,镜下组织病理改变轻微,肠道菌群无明显紊乱。结论：双歧杆菌对溃疡性结肠炎发生有预防作用,并能减轻症状和病变。     

Colonic vasoactive intestinal polypeptide in ulcerative colitis

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is localised in both the central and peripheral nervous system. In the human colon VIP is found in all layers and the highest concentrations have been found in the myenteric plexus. It is known that VIP has various effects on intestinal functions: i) it is a potent stimulant of mucosal water and electrolyte secretion: ii) it is involved in the peristaltic reflex: and iii) plays an inhibitory role on immune cell function. Based on these biological effects it has been hypothesized that the intestinal mucosal immune system and inflammation may be influenced by alterations in the tissue concentrations of VIP. Some authors have demonstrated no changes in the VIP colonic content of patients with ulcerative colitis, whereas others have demonstrated a reduction. Our results, using specific radioimmunoassay, showed that there is a significant decrease of VIP in both rectal and colonic mucosa of patients with ulcerative colitis as compared to controls. The VIP decrease is selective since substance P and calcitonin gene-related peptide were unchanged in the mucosal tissue of ulcerative colitis patients and furthermore the VIP alteration is correlated to the degree of mucosal inflammation. These findings suggest that the reduction of VIP mucosal content, even if it represents a non-specific event, could influence local inflammatory response and the activity of the disease.     

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin--peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their α-2,6 or α-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy     

Drug therapy: dose-response relationship of oral mesalazine in inflammatory bowel disease.

Mesalazine is widely used in the treatment of inflammatory bowel disease. Little is known about the dose-response relationship and about possible dose related side effects. In ulcerative colitis higher dosages of mesalazine (3 g) are more effective in maintaining a remission than lower dosages (1.5 g). In mild to moderately active ulcerative colitis, studies also indicate that higher dosages might be more effective in inducing remission. Dose-comparing studies in Crohn''s disease are even more sparse, but the available results indicate higher efficacy at higher dose levels. None of the known side effects of mesalazine are clearly dose-related. A pH-dependent release system, however, can cause a sudden release of high doses of mesalazine. Consequent peak levels in serum have been implicated in mesalazine induced nephrotoxicity. In conclusion, despite the current practice of using increasing dosages of mesalazine in inflammatory bowel disease, both efficacy and safety have been established tentatively.     

Beneficial and preventive effect of chitin nanofibrils in a dextran sulfate sodium-induced acute ulcerative colitis model

Chitin nanofibrils, which are prepared from dried crab shells by a grinding method, are newly developed natural materials with uniform widths of approximately 10-20 nm. The bioactivities of chitin nanofibrils have not been investigated. In this study, we examined the preventive effects of chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis. The results indicated that chitin nanofibrils improved clinical symptoms and suppressed ulcerative colitis. Furthermore, chitin nanofibrils suppressed myeloperoxidase activation in the colon and decreased serum interleukin-6 concentrations. Conversely, chitin powder did not suppress DSS-induced acute ulcerative colitis. Our results suggested that chitin nanofibrils have potential as a functional substance for inflammatory bowel disease patients.     

An antibiotic-responsive mouse model of fulminant ulcerative colitis

Background

The constellation of human inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn''s disease, which both display a wide spectrum in the severity of pathology. One theory is that multiple genetic hits to the host immune system may contribute to the susceptibility and severity of IBD. However, experimental proof of this concept is still lacking. Several genetic mouse models that each recapitulate some aspects of human IBD have utilized a single gene defect to induce colitis. However, none have produced pathology clearly distinguishable as either ulcerative colitis or Crohn''s disease, in part because none of them reproduce the most severe forms of disease that are observed in human patients. This lack of severe IBD models has posed a challenge for research into pathogenic mechanisms and development of new treatments. We hypothesized that multiple genetic hits to the regulatory machinery that normally inhibits immune activation in the intestine would generate more severe, reproducible pathology that would mimic either ulcerative colitis or Crohn''s disease.

Methods and Findings

We generated a novel mouse line (dnKO) that possessed defects in both TGFβRII and IL-10R2 signaling. These mice rapidly and reproducibly developed a disease resembling fulminant human ulcerative colitis that was quite distinct from the much longer and more variable course of pathology observed previously in mice possessing only single defects. Pathogenesis was driven by uncontrolled production of proinflammatory cytokines resulting in large part from T cell activation. The disease process could be significantly ameliorated by administration of antibodies against IFNγ and TNFα and was completely inhibited by a combination of broad-spectrum antibiotics.

Conclusions

Here, we develop to our knowledge the first mouse model of fulminant ulcerative colitis by combining multiple genetic hits in immune regulation and demonstrate that the resulting disease is sensitive to both anticytokine therapy and broad-spectrum antibiotics. These findings indicated the IL-10 and TGFβ pathways synergize to inhibit microbially induced production of proinflammatory cytokines, including IFNγ and TNFα, which are known to play a role in the pathogenesis of human ulcerative colitis. Our findings also provide evidence that broad-spectrum antibiotics may have an application in the treatment of patients with ulcerative colitis. This model system will be useful in the future to explore the microbial factors that induce immune activation and characterize how these interactions produce disease.     

Colonic mucins in ulcerative colitis: evidence for loss of sulfation

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [³⁵S] sulfate and [³H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by -elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed >90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.Abbreviations WGA wheat germ agglutinin - UC ulcerative colitis - HRP horseradish peroxidase     

复方苦参汤联合美沙拉嗪对溃疡性结肠炎治疗效果及炎性因子水平的影响

目的:探讨复方苦参汤联合美沙拉嗪对溃疡性结肠炎治疗效果及炎性因子水平的影响。方法:以我院2017年1月至2019年12月中西医结合科和消化内科收治的206例溃疡性结肠炎患者为研究对象,根据随机抽样法将受试者分为对照组和研究组,每组各103例,对照组接受美沙拉嗪治疗,研究组在对照组的基础上口服复方苦参汤治疗,比较两组的治疗总有效率,治疗前后黏膜病变、疾病活动指数与各炎性因子水平变化以及用药安全性。结果:研究组治疗总有效率较对照组高(P<0.05);治疗后两组肠镜下黏膜病变与疾病活动指数较治疗前均明显改善,且研究组显著优于对照组(P<0.05);治疗后两组白细胞介素(interleukine,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor, TNF)-α、C反应蛋白(C-reactive protein,CRP)及降钙素原(procallcitonin,PCT)等炎性因子水平较治疗前均显著下降,且研究组低于对照组(P<0.05);两组药物所致不良反应发生率比较无统计学差异(P>0.05)。结论:复方苦参汤联合美沙拉嗪可有效缓解临床症状,改善肠道黏膜病变,降低肠道炎性反应,控制病情进展,疗效安全显著,对促进溃疡性结肠炎患者病情康复具有积极意义。