溃结灵对溃疡性结肠炎大鼠结肠黏膜NF-κB DNA结合活性的作用

目的:观察溃疡性结肠炎(UC)大鼠结肠黏膜核因子-κB(NF-κB)DNA结合活性的变化特点及溃结灵对其的影响.方法:采用三硝基苯磺酸(TNBS)法制作UC大鼠模型,大鼠随机分为以下六组:正常对照组、模型对照组、溃结灵低、中、高剂量组、阳性药柳氮磺胺吡啶(SASP)组.治疗10d后处死大鼠,取新鲜结肠黏膜标本提取核蛋白,利用以ELISA为基础的Trans AM TM NFκB p65试剂盒检测NF-κB相对活性并进行统计学分析.结果:模型组结肠黏膜NF-κB相对活性明显高于正常组(0.440±0.119 vs 0.261±0.042,P＜0.01);溃结灵高剂量组和SASP组结肠黏膜NF-κB相对活性(0.26 1±0.056,0.269±0.106)明显低于模型组(P＜0.01).结论:NF-κB参与了UC大鼠的发病过程,渍结灵使TNBS法UC大鼠模型结肠黏膜NF-κB相对活性明显降低,这可能是其治疗UC作用的机制之一.     

溃结康泰治疗溃疡性结肠炎的临床研究

目的：观察溃结康泰治疗溃疡性结肠炎的临床疗效。方法：对纤维结肠镜检查确诊的溃疡性结肠炎６４例应用溃结康泰治疗,５６ 例应用柳氮磺胺吡啶加甲硝唑治疗,并进行疗效对照观察。结果：溃结康泰组近期治愈率、总有效率分别为６４．０６％ 、９３．７４％ ;对照组分别为４１．０７％ 、８０．３５％ ,两组间近期治愈率、总有效率比较有极显著性差异（Ｐ＜ ０．０１）。随访２～４ 年,溃结康泰组复发率为１８．１８％ （６／３３）,对照组为５３．３０％ （１６／３０）,两组远期疗效比较有极显著性差异（Ｐ＜ ０．０１）。结论：溃结康泰治疗溃疡性结肠炎疗效可靠且副作用少。     

TLR2在溃疡性结肠炎患者结肠黏膜中的表达

目的 检测溃疡性结肠炎(UC)患者结肠肠黏膜TLR2蛋白及TLR2 mRNA的表达及其与UC临床活动度、内镜分级的关系.方法 取47例UC患者结肠黏膜标本根据内镜及临床活动度进行分级,同时收集正常对照者结肠黏膜标本13例.用Western Blot技术和半定量反转录聚合酶链反应方法(RT-PCR)检测结肠黏膜中TLR2蛋白及TLR2 mRNA的表达.结果 UC患者结肠黏膜TLR2蛋白及TLR2mRNA的表达量高于正常对照者,且随着内镜下及临床病变分级的加重逐渐增加.结论 UC患者肠黏膜中TLR2及TLR2 mRNA的表达增加,且其表达均随临床及内镜下病变程度加重,表达逐渐增加,在一定程度上可以反映疾病的活动度.     

溃结康泰治疗溃疡性结肠炎的临床研究

目的 观察溃结康泰治疗溃疡性结肠炎的临床疗效。方法 对纤维结肠镜检查确诊的溃疡性结肠炎６４例应用溃结康泰治疗,５６例应用柳氮碘胺吡啶加甲硝唑治疗,并进行疗效对照观察。结果 溃结康泰组近期治愈率、总有效率分别为６４．０６％、９３．７％;对照组分别为４１．０７％、８０．３５％,两组间近期治愈率、总有效率比较有极显著性差异（Ｐ〈０．０１）。随访２～４年,溃疡康秦组复发率为１８．１８％（６／３３）,对照组     

TLRs在溃疡性结肠炎小鼠结肠中的表达研究

目的 观察溃疡性结肠炎（UC）小鼠模型结肠组织中TLR2、TLR4和TLR9的表达情况,为UC发病机制的研究提供新思路.方法 将6～8周龄健康雄性BALB/c小鼠随机分为两组：正常对照组（n=10）和UC模型组（n=10）,正常对照组小鼠蒸馏水自由饮用7d.UC模型组小鼠5％ DSS溶液自由饮用7d造模.7d后处死小鼠,采用实时荧光定量PCR方法检测各组小鼠结肠黏膜组织中TLR2、TLR4和TLR9 mRNA的表达情况.结果 正常对照组结肠组织中无TLR2、TLR4和TLR9 mRNA的表达,而UC组结肠组织中TLR2、TLR4和TLR9 mRNA表达明显,两组比较差异有统计学意义（P＜0.05）.结论 TLR2、TLR4、TLR9可能参与了UC的发病过程.     

大肠湿热型溃疡性结肠炎患者防御素和白细胞介素8表达及溃结灵的干预作用

[目的]探讨防御素(Human defensins,HNP1-3)和白细胞介素8(IL-8)在大肠湿热型溃疡性结肠炎(UC)结肠组织中的表达及两者之间的相关性,观察中药溃结灵煎剂对HNP1-3和IL-8的影响,探讨溃结灵治疗UC的作用机制。[方法]60例活动期UC(大肠湿热型)患者随机分为治疗组[溃结灵加柳氮磺胺吡啶(SASP)]、对照组各30例,采用常规免疫组化SP法检测2组治疗前后肠黏膜组织内HNP1-3及IL-8的蛋白表达情况。[结果]UC患者随着病变分级程度的增高,HNP1-3、IL-8细胞因子的表达逐渐增强。两者呈明显的正相关。2组治疗后自身比较HNP1-3、IL-8表达较治疗前明显减少(P0.01,0.05)。2组治疗后HNP1-3、IL-8差值比较差异有统计学意义(P0.05)。[结论]溃结灵配合SASP治疗UC很可能是通过抑制IL-8等细胞因子对中性粒细胞的激活,不能或减少释放细胞毒性HNP1-3,使损伤的内皮细胞得以修复,继而达到治疗的目的。     

溃结康胶囊治疗溃疡性结肠炎的临床研究

溃疡性结肠炎是一种病因未明的炎症性肠病,亦是一种癌前期状态。笔者自１９９４年５月～１９９８年３月应用溃结康胶囊治疗溃疡性结肠炎１２８例,并设阳性对照组１０４例进行对照观察,现报告如下。１　资料与方法１．１　临床资料：所选病例均为本院门诊患者,均参照中华全国中医学会肛肠学会１９８７年制定的溃疡性结肠炎诊治标准［１］,根据临床症状、体征、肠镜病理检查、粪便常规、粪便细菌培养等进行诊断。按就诊次序随机将病例分为治疗组和对照组。治疗组１２８例,男７２例,女５６例;年龄７～７３岁,平均３６．７岁;病程２个…     

溃结汤治疗溃疡性结肠炎合并糖尿病25例疗效观察

目的观察溃结汤治疗溃疡性结肠炎合并糖尿病的临床疗效。方法将该院2009年1月—2014年5月收治的溃疡性结肠炎合并糖尿病患者45例,随机分为观察组25例,给予患者溃结汤进行治疗;对照组20例,给予口服柳氮磺吡啶片进行治疗,观察两组的治疗效果。结果通过治疗,观察组治愈12例,显效6例,有效5例,无效2例,总有效率92.00%;对照组治愈2例,显效3例,有效10例,无效5例,总有效率75.00%。两组差异有统计学意义。结论溃结汤治疗溃疡性结肠炎,安全性高效果满意。     

溃结灵颗粒治疗活动期溃疡性结肠炎的临床与实验研究

目的：通过临床和动物实验探讨溃结灵治疗溃疡性结肠炎(UC)的机制。方法：活动期UC(湿热内蕴证)患者92例随机分为溃结灵组、柳氮磺胺吡啶组(SASP)和中西药结合组，以肠粘膜病变、中医证候疗效、主要症状积分作为观察指标；免疫法造成UC大鼠模型，随机分成空白对照组，SASP组，溃结灵高、中、低剂量组(每组10只)及正常组，作结肠病理观察和血清肿瘤坏死因子-α(TNF-α)和白细胞介素—6(1L—6)的检测。结果：溃结灵组对患者的粘膜疗效与SASP组比较差异无显著性意义，但证候疗效明显优于SASP组(P＜0．01)，总有效率为93．33％；对改善腹泻、腹痛、腹胀、里急后重的作用优于SASP组，且无任何不良反应。溃结灵能减轻UC大鼠炎症，改善粘膜病变，并能减少TNF—α。结论：溃结灵具有确切的治疗UC的作用，这可能与它能减轻炎症、调节炎症因子有关。     

神经激肽-1受体在溃疡性结肠炎黏膜中的表达

目的：了解神经激肽-1受体(NK-1R)在溃疡性结肠炎(UC)病人结肠活检黏膜中的表达，探讨该受体的表达与UC严重程度的关系。方法：38个UC黏膜标本取自因该病而行结肠镜检查的病人，男23例，女15例；对照组结肠黏膜取自15例肠易激综合征(IBS)病人，男8例，女7例。应用逆转录聚合酶链反应(RT-PCR)检测对照组和UC肠黏膜NK-1R的mRNA表达水平，应用Western blot技术检测NK-1R的蛋白水平，以免疫组化方法进行NK-1R的组织学定位。结果：与对照组肠黏膜相比，UC黏膜中NK-1R mRNA和蛋白都过度表达，NK-1R mRNA的表达与疾病的严重程度相关。免疫组化检查显示，NK-1R的表达主要位于UC的肠黏膜表面、黏膜固有层的单核细胞、黏膜下层的动静脉等处。结论：UC黏膜组织中NK-1R的表达水平明显上调，扰乱了神经激肽的作用环节，加剧了肠黏膜的病理改变。     

Bactericidal/permeability-increasing protein in colonic mucosa in ulcerative colitis.

BACKGROUND/AIMS: Increased mucosal concentration of bactericidal/permeability-increasing protein (BPI) has been shown in inflammatory bowel diseases. The purpose of the present study was to investigate the relationship between the mucosal concentration of BPI and the grade of mucosal inflammation in ulcerative colitis. METHODOLOGY: Samples of colonic mucosa from 12 patients with ulcerative colitis and from 8 control patients were studied. The concentration of BPI in tissue extracts was measured by a time-resolved fluoroimmunoassay. The concentration of BPI was compared between samples with histological inflammatory changes of different severity. BPI was localized in tissue sections by immunohistochemistry. RESULTS: The concentration of BPI was higher (p < 0.001) in samples of colonic mucosa from patients with ulcerative colitis (median: 3.2 micrograms/g, range: 0.3-22.6 micrograms/g) than in control samples (0.4 microgram/g, 0.1-0.6 microgram/g,). Moreover, the concentration of BPI was higher (p = 0.015) in samples with severe inflammation (2.5 mu/g, 0.3-22.6 micrograms/g) than in those with mild inflammation (0.5 mu/g, 0.3-2.5 micrograms/g). The concentration of BPI in mucosal samples correlated well with the degree of histological inflammation (Spearman R = 0.70, p = 0.01). BPI was localized in polymorphonuclear leukocytes in the mucosa and stroma of the colonic wall. CONCLUSIONS: The concentration of BPI is increased in the colonic mucosa of patients with ulcerative colitis. The increase in the concentration of BPI in colonic mucosa seems to be closely associated with the inflammatory activity of ulcerative colitis.     

Urocortin 1 in colonic mucosa in patients with ulcerative colitis

Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry and mRNA in situ hybridization. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group. Ucn1 mRNA was expressed in lamina propria plasma cells, and both corticotropin-releasing factor(1) and corticotropin-releasing factor(2(a)) mRNAs were also partially coexpressed in these cells and macrophages. The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.     

Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis.

Short-chain fatty acid irrigation has been shown to ameliorate inflammation in diversion colitis. In this study the effect of butyrate enemas was tested in 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L) and 2 weeks with placebo in random order (single-blind trial). Before and after treatment, clinical symptoms were noted and the degree of inflammation was graded endoscopically and histologically. Rectal proliferation was assessed by autoradiography. After butyrate irrigation, stool frequency (n/day) decreased from 4.7 +/- 0.5 to 2.1 +/- 0.4 (P less than 0.01) and discharge of blood ceased in 9 of 10 patients. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8 (P less than 0.01). The histological degree of inflammation decreased from 2.4 +/- 0.3 to 1.5 +/- 0.3 (P less than 0.02). Overall crypt proliferation was unchanged, but the upper crypt-labeling index fell from 0.086 +/- 0.019 to 0.032 +/- 0.003 (P less than 0.03). On placebo, all of these parameters were unchanged. These data support the view that butyrate deficiency may play a role in the pathogenesis of distal ulcerative colitis and that butyrate irrigation ameliorates this condition.     

Lymphatic vessels in the colonic mucosa in ulcerative colitis

In the normal colonic mucosa, lymphatics are found only in a narrow band associated with the muscularis mucosae and are absent from the rest of the mucosa. This study examined whether this arrangement of lymphatics is also valid in ulcerative colitis. Histological sections of colon from 15 long-standing cases were investigated with antibodies against CD 34 (negative for lymphatics; positive for blood vessel endothelium) and, in selected cases, podoplanin (positive for lymphatic endothelium; negative for blood vessel endothelium). Whereas inflammation of the mucosa was not associated with changes in lymphatics, an increase in intramucosal lymphatics was seen when the pathological changes included widening of the muscularis mucosae or penetration of the mucosa by muscle fibers, filiform changes in the mucosa, and hyperplasia of the mucosa-associated lymphoid tissue (MALT). In specimens with epithelial dysplasia, an association between the dysplastic epithelium and ectatic and quantitatively increased lymphatics was observed. With superimposed carcinoma, no relationship between the malignant tumor and lymphatics was identifiable. Nevertheless, pre-existing lymphatics in the muscularis mucosae were involved in lymphatic tumor spread. The immunohistochemical findings demonstrated that lymphatics occurred in all areas of the mucosa in ulcerative colitis (or, in effect, at sites which were not normally found under physiological conditions) and in regions that favored lymphatic tumor dissemination. Whether these lymphatics were actually involved in metastasis remains to be defined.     

Tissue-type plasminogen activator of colonic mucosa in ulcerative colitis

Microvascular endothelial alterations are thought to be a crucial step for development of hemorrhagic changes in various pathological states. In this study, we determined the activity and amount of tissue-type plasminogen activator (t-PA) in the biopsy specimens from sigmoid colon of patients with ulcerative colitis to evaluate endothelial alterations and vascular changes of permeability. The results of this investigation revealed that mucosal amount of t-PA in the active stage of ulcerative colitis was two- to threefold higher than in healthy controls, while t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to correlate well to the degree of inflammation of colonic mucosa, and t-PA amount was still increased in the inactive stage. The present study indicates that t-PA determination in colonic biopsy specimens may be useful for the evaluation of clinical activity of ulcerative colitis in terms of the mucosal microvascular endothelial changes.This work was supported by the grant from the Japanese Ministry of Education No. 63440033 and by the grant from Keio University, School of Medicine.     

Increased protein tyrosine kinase activity of the colonic mucosa in ulcerative colitis.

The protein tyrosine kinase (PTK) activity was measured in the inflamed colonic mucosa of 12 patients with ulcerative colitis and in the normal colonic mucosa of 12 control patients with colon cancer. The specific PTK activity in the particulate fraction obtained from ulcerative colitis mucosa was significantly increased compared with that of normal mucosa (5.10 +/- 0.60 pmol/min/mg versus 2.12 +/- 0.44 pmol/min/mg protein; p less than 0.05). Inflamed ulcerative colitis mucosa also showed a significantly higher total PTK activity in the particulate fraction than normal mucosa (2.60 +/- 0.42 pmol/min/g versus 0.91 +/- 0.16 pmol/min/g tissue; p less than 0.05). Mucosal samples from ulcerative colitis patients were divided into those with mild and those with severe inflammation on histologic examination (n = 6 each). The particulate PTK activity of severely inflamed mucosa was significantly higher than that of mildly inflamed mucosa (p less than 0.05). These results suggest that colonic inflammation in ulcerative colitis is associated with alterations in cellular PTK activity.