复方青黛颗粒对溃疡性结肠炎模型大鼠结肠toll样受体2,4基因表达的影响

[目的]观察复方青黛颗粒对溃疡性结肠炎（UC）模型大鼠结肠toll样受体2,4（TLR2,TLR4）基因表达的影响,探讨其治疗UC的可能作用机制。[方法]用三硝基苯磺酸（TNBS）制备UC大鼠模型,将52只SD实验大鼠随机分为正常对照（空白）组、模型组、柳氮磺胺吡啶（SASP）组（500 mg/kg）,复方青黛颗粒低（600 mg/kg）、中（900 mg/kg）、高（1 200 mg/kg）剂量组,从造模后第3天开始分别每天灌胃给药1次至实验结束,第14 d（灌胃10 d后）,用逆转录聚合酶链反应（RT-PCR）法检测TLR2、TLR4的基因表达水平。[结果]模型组TLR2、TLR4基因相对表达量均明显高于空白组（P〈0.01）;复方青黛颗粒中、高剂量组TLR2相对表达量及高剂量组TLR4相对表达量与SASP组比较差异均无统计学意义,但均明显低于模型组（均P〈0.05）。[结论]复方青黛颗粒能有效治疗TNBS诱导的UC模型大鼠,可能与复方青黛颗粒抑制TLR2、TLR4基因表达有关。     

复方青黛颗粒对溃疡性结肠炎模型大鼠结肠组织TGF-β1和VEGF表达影响

[目的]观察复方青黛颗粒对溃疡性结肠炎(UC)大鼠结肠组织转化生长因子-β1(TGF-β1)与血管内皮生长因子(VEGF)表达的影响,进一步探讨复方青黛颗粒治疗UC的相关机制。[方法]三硝基苯磺酸(TNBS)法制备大鼠UC模型,随机分为空白对照组、模型对照组、柳氮磺吡啶(SASP)组及复方青黛颗粒低、中、高剂量组。治疗结束后取大鼠结肠组织,用RT-PCR方法检测TGF-β1及VEGF mRNA表达。[结果]与空白对照组比较,模型对照组TGF-β1及VEGF基因表达明显增高(P0.05),复方青黛颗粒高剂量组TGF-β1基因表达较模型对照组显著下降(P0.05),VEGF基因表达较模型对照组显著升高(P0.05)。[结论]复方青黛颗粒对TNBS诱导的UC大鼠的治疗作用可能与下调TGF-β1过度表达及上调VEGF有关。     

复方青黛颗粒对大鼠溃疡性结肠炎模型的影响

目的 :观察复方青黛颗粒对大鼠溃疡性结肠炎模型的影响 ,为临床用药的有效性提供实验依据。方法 :采用异种异体结肠粘膜组织致敏法。将 SD大鼠随机分为空白对照组 ,模型对照组 ,复方青黛颗粒高、中、低剂量组 ,泻痢消胶囊组。连续给药 4周。空白对照组和模型对照组灌胃给予等量生理盐水 ;末次给药后 2 4 h,大鼠眼眶采血 ,测定乳酸脱氢酶和淀粉酶含量 ;处死大鼠 ,计数全结肠溃疡点和充血点 ;称结肠湿重 ,计算肠重指数。结果 :复方青黛颗粒 3个剂量组大鼠的溃疡数和充血指数显著减少或降低 ,与模型对照组比较差异有非常显著性意义 (P <0 .0 1) ,各剂量组大鼠的结肠重量和肠重指数 ,都有显著增加 ,中、高两剂量组与模型对照组比较差异有显著性意义(P <0 .0 5 ,<0 .0 1) ;血清乳酸脱氢酶含量较模型对照组有降低趋势 (P >0 .0 5 ) ,复方青黛颗粒组均有使模型动物降低的血清淀粉酶含量明显恢复的作用 ,与模型对照组比较差异有显著性意义 (P <0 .0 5或 <0 .0 1)。结论 :复方青黛颗粒对溃疡性结肠炎模型大鼠有显著的治疗作用     

复方青黛颗粒对溃疡性结肠炎模型大鼠结肠MMP-1及TIMP-1表达的影响

[目的]观察复方青黛颗粒对溃疡性结肠炎（UC）模型大鼠结肠基质金属蛋白酶1（MMP-1）及其特异性组织抑制因子（TIMP-1）基因表达的影响,探讨其治疗UC的作用机制.[方法]用三硝基苯磺酸（TNBS）制备UC大鼠模型,将52只SD大鼠随机分为正常对照（空白）组、模型组、美沙拉嗪（5-ASA）组,复方青黛颗粒低、中、高剂量组,从造模后第3天开始分别每天灌胃给药1次至实验结束,第14天（灌胃10 d后）,用逆转录聚合酶链反应（RT-PCR）法检测MMP-1、TIMP-1基因表达的水平.[结果]模型组MMP-1、TIMP-1基因相对表达量均明显高于空白组（P＜0.05）;复方青黛颗粒中、高剂量组MMP-1相对表达量及中、高剂量组和5-ASA组TIMP-1相对表达量均明显低于模型组（均P＜ 0.05）.[结论]复方青黛颗粒能有效治疗TNBS诱导的UC模型大鼠,可能与复方青黛颗粒抑制MMP-1、TIMP-1基因表达有关.     

复方青黛颗粒联合路优泰治疗溃疡性结肠炎的疗效观察

[目的]观察复方青黛颗粒联合路优泰治疗溃疡性结肠炎(UC)的疗效。[方法]选取我科近3年病房收治的UC伴焦虑患者,将其分为复方青黛颗粒联合路优泰治疗组和复方青黛颗粒对照组,比较2组的疗效。[结果]治疗组和对照组疗效比较,差异具有统计学意义(P<0.05)。[结论]对于伴有焦虑的UC患者在治疗时给予抗焦虑药物具有一定的临床治疗意义。     

青黛颗粒对溃疡性结肠炎实验大鼠血清白细胞介素6和10水平的影响

[目的]观察青黛颗粒对溃疡性结肠炎（UC）实验大鼠血清白细胞介素6（IL-6）和白细胞介素10（IL-10）水平的影响,探讨其治疗UC可能的作用机制。[方法]将52只SD大鼠采用三硝基苯磺酸（TNBS）法制备UC大鼠模型。造模结束后第2天取4只大鼠处死确定造模成功,余48只随机均分为6组：正常组,模型组,柳氮磺胺嘧啶（SASP）阳性药物治疗（SASP）组,青黛颗粒低、中、高剂量组,各8只。造模后第3天开始各组动物灌胃给药,连续给药10 d,实验第14天通过腹主动脉采血取血清,用ELISA法测定血清IL-6、IL-10水平。[结果]青黛颗粒低、中、高3个剂量组与模型组比较,血清IL-6水平显著降低,IL-10水平升高（P〈0.01）;青黛颗粒高剂量组血清IL-6I、L-10水平变化与SASP组比较,差异无统计学意义（P〉0.05）。[结论]青黛颗粒治疗实验性UC的作用机制可能与降低IL-6水平,升高IL-10水平有关。     

单味青黛口服治疗溃疡性结肠炎的思考

溃疡性结肠炎(ulcerative colitis,UC)是一种以发作和缓解交替为特征的炎症性肠疾。其治疗目标是诱导和维持缓解,控制临床症状,促进黏膜愈合,达到良好预后[1]。目前UC主要依赖于5-氨基水杨酸、类固醇激素、免疫抑制剂和生物制剂等药物治疗,然而对这些药物的依赖、耐药、不耐受、反应丧失、机会性感染正日益成为新的临床问题,同时缓解率在临床试验中并不令人满意,因此许多炎症性肠病(inflammatory bowel disease,IBD)患者、临床医生和研究人员正在更多地关注补充和替代医学(CAM)[2-3],在北美和欧洲的研究中,目前或过去使用CAM治疗IBD的比例为21%~60%[4-5]。     

抑郁症对大鼠结肠iNOS、NO和COX-2的影响

目的　观察抑郁症对大鼠结肠组织诱导型一氧化氮合酶 (iNOS)、一氧化氮 (NO)含量和环氧合酶 2 (COX 2 )表达的影响。方法　制备经典的大鼠抑郁模型。采用生物化学试剂盒检测大鼠结肠组织中iNOS和NO的含量 ,免疫组化SP方法检测结肠组织COX 2的表达。结果　抑郁模型大鼠结肠组织中iNOS和NO的含量均升高 (P <0 .0 1) ;COX 2在抑郁大鼠结肠中表达升高 (P<0 .0 1)。结论　抑郁症对大鼠结肠组织的损伤可能通过改变iNOS和NO的含量 ,及COX 2的表达实现的     

复方青黛颗粒对溃疡性结肠炎大鼠NF-κBP65、TNF-α表达的影响

目的:探讨复方青黛颗粒治疗溃疡性结肠炎(UC)大鼠的相关机制.方法:用三硝基苯磺酸(TNBS)法制备大鼠UC模型,分为空白对照组、模型对照组、柳氮磺吡啶(SASP)组、复方青黛颗粒低、中、高剂量组.造模后第3天开始灌胃给药,共给药10d,实验第14天,处死大鼠.取大鼠结肠组织及血清,用免疫组织化学SP法检测NF-κBP65蛋白表达,ELISA测定血清中肿瘤坏死因子α(TNF-α)的含量.结果:空白对照组与模型对照组比较,结肠组织中NF-κBP65蛋白表达及血清中TNF-α表达明显增高(0.276±0.0081vs0.138±0.003;67.657±3.580vs18.990±3.964,均P<0.05)复方青黛颗粒高剂量组与模型对照组相比,结肠组织中NF-κBP65蛋白表达及血清中TNF-α表达显著降低(0.217±0.007vs0.276±0.008;27.783±2.867vs67.657±3.580,均P<0.05).结论:复方青黛颗粒对TNBS诱导的UC大鼠的治疗作用可能与通过NF-κB信号传导通路调节TNF-α含量有关.     

维药西帕依溃结安在大鼠溃疡性结肠炎模型中对iNOS基因表达的影响

目的:检测维药西帕依溃结安对大鼠溃疡性结肠炎模型中诱导型一氧化氮合酶(iNOS)基因表达的影响,探讨药物的可能作用机制.方法:采用2,4-二硝基氯苯(DNCB)复合乙酸法构建溃疡性结肠炎大鼠模型,建立维药西帕依溃结安大、中、小剂量干预组及生理盐水阴性对照组(NS组),应用半定量RT-PCR和Western blot方法检测各组中iNOS mRNA和蛋白质的表达水平.结果:与NS组相比,维药西帕依溃结安各干预组iNOS mRNA表达水平无统计学意义,iNOS蛋白表达水平下调,差异有统计学意义(0.44±0.40 vs 1.00±0.07,P<0.05).结论:维药西帕依溃结安治疗溃疡性结肠炎可能是通过在转录后水平上调节iNOS的表达而发挥作用.     

Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis

BACKGROUND: Decreased synthesis of the predominant secretory human colonic mucin (MUC2) occurs during active ulcerative colitis. AIMS: To study possible alterations in mucin sulphation and mucin secretion, which could be the cause of decreased mucosal protection in ulcerative colitis. METHODS: Colonic biopsy specimens from patients with active ulcerative colitis, ulcerative colitis in remission, and controls were metabolically labelled with [35S]-amino acids or [35S]-sulphate, chase incubated and analysed by SDS-PAGE, followed by quantitation of mature [35S]-labelled MUC2. For quantitation of total MUC2, which includes non-radiolabelled and radiolabelled MUC2, dot blotting was performed, using a MUC2 monoclonal antibody. RESULTS: Between patient groups, no significant differences were found in [35S]-sulphate content of secreted MUC2 or in the secreted percentage of either [35S]-amino acid labelled MUC2 or total MUC2. During active ulcerative colitis, secretion of [35S]-sulphate labelled MUC2 was significantly increased twofold, whereas [35S]-sulphate incorporation into MUC2 was significantly reduced to half. CONCLUSIONS: During active ulcerative colitis, less MUC2 is secreted, because MUC2 synthesis is decreased while the secreted percentage of MUC2 is unaltered. Furthermore, sulphate content of secreted MUC2 is unaltered by a specific compensatory mechanism, because sulphated MUC2 is preferentially secreted while sulphate incorporation into MUC2 is reduced.     

MUC2 is the prominent colonic mucin expressed in ulcerative colitis.

BACKGROUND--It has been shown that MUC2 is the prominent mucin synthesised in healthy colon. AIM--To identify the predominant mucins in ulcerative colitis (UC) and to study their biosynthesis. METHODS AND RESULTS--Mucin was purified from UC resection specimens. This mucin on sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) presented as one, high molecular weight, periodic acid/Schiff's reagent (PAS) stainable band. Amino acid composition showed a close resemblance to that of MUC2. Immunoprecipitation with a specific anti-MUC2 antiserum confirmed that this mucin was MUC2. In addition, on the mRNA level MUC2 was also the most prominent mucin expressed in UC. Polyclonal antiserum was elicited, mainly recognising mucin peptide epitopes of UC and normal colonic mucin. Biosynthetic studies with [35S]amino acids showed that the MUC2-precursor in UC displayed a molecular mass on SDS-PAGE of approximately 600 kDa. This precursor was converted into a mature MUC2 with anomalous mobility on SDS-PAGE of 550 kDa and was secreted. Only this 550 kDa band could be labelled with [35S]sulphate and stained by PAS. CONCLUSIONS--This study shows that in parallel with the mucin expression in healthy controls, MUC2 is the major mucin expressed in UC. Qualitatively, MUC2 biosynthesis seems unchanged in UC.     

PPAR-γ在溃疡性结肠炎粘膜中的表达

目的了解过氧化物酶增生激活受体（ＰＰＡＲ－γ）在溃疡性结肠炎（ＵＣ）患者结肠活检粘膜中的表达及其与疾病严重度的关系。方法　采用免疫组化法测定３１例ＵＣ患者和１２例对照组的结肠活检粘膜中ＰＰＡＲ－γ的表达情况。结果　ＵＣ患者受累及相对正常的结肠上皮ＰＰＡＲ－γ的表达均较正常对照组下降，三组分别为２４．７％±１．４９％、４３．８％±２．０３％、７０．２％±３．７５％（Ｐ＜０．０５），且病变越重，表达越低。结论ＵＣ患者内镜下活检粘膜中ＰＰＡＲ－γ的表达下降，并与疾病严重程度成负相关，提示其可能与ＵＣ的发病有关。     

Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis

BACKGROUND AND AIM: The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. METHODS: Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. RESULTS: In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. CONCLUSION: There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC.     

Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma

AIM:To study the expression profiles of MUC2 and MUC5AC in tumorigenesis of colorectal carcinoma and in its different pathologic types.METHODS:Formalin-fixed,paraffin-embedded human colorectal tissue specimens were immunostained with antibodies against MUC2 and MUC5AC.Six samples of normal mucosa(NM),12 samples of hyperplastic polyp(HP),15 samples of tubular adenoma with low-grade dysplasia(LGD),14 samples of tubular adenoma with high-grade dysplasia(HGD),26 samples of conventional colorectal adenocarcinoma...     

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.