溃疡性结肠炎大肠的结肠电和动力异常及中药胃肠康的？…

以二硝基氯地制作大鼠溃疡性结肠炎模型，埋藏电极记录结肠电，观察中药复方胃肠康的作用，并以“离体肠道流体推进检测系统”观察胃肠康成分白术羟内酯和二氢黄酮Ｂ３对病模大鼠结肠推进行为的影响。发现病模大鼠结肠发生典型的溃疡，浸泡液一氧化氮（ＮＯ）产物ＮＯＰ的含量显著高于正常；其结肠的基本电节为慢、幅值降低、收缩性复合民及电明显减少；离体结肠动力异常并表现为复合波频率异常增高、肛向纯推进过高及动力减弱３个类     

5,7-二羟基双氢黄酮治疗大鼠糖尿病胃肠神经功能紊乱效果观察

目的 评价5,7-二羟基双氢黄酮对糖尿病大鼠胃肠道功能的作用.方法 采用链脲佐菌素诱发糖尿病大鼠胃肠神经功能紊乱模型,予5,7-二羟基双氢黄酮1、3、9 mg/kg灌胃,测定模型血糖、胃肠慢波电位、小肠壁内神经蛋白含量,并观察胃肠推进功能变化及胃肠对乙酰胆碱、阿托品敏感性的影响.结果 双氢黄酮各剂量组胃肠慢波电位频率下降、胃肠推进功能提高、胃肠壁内神经蛋白含量增加.结论 5,7-二羟基双氢黄酮可改善糖尿病导致的胃肠神经功能紊乱.     

酚酞对大鼠结肠动力及肠神经系统的影响研究

目的 探讨长期应用酚酞对结肠肌电及肠神经系统(ENS)的影响。方法 建立大鼠“泻剂结肠”模型，应用电生理、组化及免疫组化技术研究酚酞对大鼠结肠动力、ENS多种神经递质及Cajal间质细胞(ICC)的影响。结果 大鼠饲以酚酞3个月后，结肠慢波频率减慢，结肠肌间丛还原型烟酰胺腺嘌呤二核苷磷酸黄递酶阳性神经细胞数目增多，乙酰胆碱酯酶阳性神经细胞数目减少，一氧化氮合酶免疫反应性增强，生长抑素免疫反应性减弱，肌间丛ICC分布不均匀，突起连接杂乱。结论 长期应用酚酞对结肠动力和ENS有损害作用，在临床治疗顽固性便秘时应避免长期应用酚酞等刺激性泻剂。     

内吗啡肽对"泻剂结肠"大鼠离体肠肌条收缩反应的影响

目的研究内吗啡肽（EM）对“泻剂结肠”大鼠结肠动力的影响,以探讨慢传输性便秘（STC）的发病机制.方法以“泻剂结肠”大鼠为模型,用电刺激离体肌条收缩反应试验方法观察EM对离体肌条的影响.结果与对照组相比,EM-1和EM-2明显抑制电刺激“泻剂结肠”大鼠离体肌条收缩反应,收缩波振幅降低,对远端结肠抑制尤其明显;EM-1的抑制作用强于EM-2,这种抑制作用与浓度相关,不同浓度的Naloxone（u阿片受体拮抗剂）明显加强EM作用后电刺激“泻剂结肠”大鼠离体肌条的收缩反应,收缩波振幅增加.结论EM-1和EM-2参与“泻剂结肠”动力的调控,可能是STC发病的一个重要因素.     

糖尿病结肠动力障碍时Cajal间质细胞和干细胞因子的变化以及胰岛素的干预效应

Cajal间质细胞（ICC）异常可能是糖尿病胃肠动力障碍的重要原因之一。目的：观察糖尿病结肠慢传输型动力障碍大鼠ICC及其Kit受体配体干细胞因子（SCF）的变化，以及胰岛素干预对结肠动力障碍和ICC的影响。方法：雄性Sprague—Dawley大鼠分为正常对照组、糖尿病模型组和不同剂量胰岛素（每天8、12、16U／kg）干预组。于成模第6、8、10周时分批处死各组大鼠，以免疫组化染色、蛋白质印迹法和电子显微镜观察近端结肠组织ICC的变化．以酶联免疫吸附测定（ELISA）和荧光定量聚合酶链反应（qPCR）检测血清和结肠组织SCF的表达。结果：糖尿病模型大鼠胃肠推进率显著降低，近端结肠组织ICC数量减少，超微结构破坏，结肠组织可溶型SCF（S-SCF）mRNA表达和血清S-SCF、胰岛素水平降低。小剂量胰岛素干预可显著改善糖尿病大鼠的胃肠推进率，增加ICC数量，逆转其超微结构改变：中、大剂量胰岛素干预则无明显作用。结论：糖尿病大鼠胰岛素分泌减少，使S-SCF表达降低，引起结肠组织ICC数量减少．结构破坏，可能是结肠慢传输型动力障碍的发生基础之一。小剂量胰岛素可改善糖尿病大鼠的ICC病变和结肠动力障碍。     

实验性脾虚证结肠动力肌胃肠肽和一氧

目的观察大鼠在脾虚和应激状态下结肠动力及结肠组织内P物质(SP)、血管活性肠肽(VIP)和神经型一氧化氮合酶(nNOS)改变及治疗后变化.方法实验随机分为五组正常组、脾虚组、自然恢复组、治疗组、冷应激组;其中治疗组以加味四君子汤治疗.实验采用银球三电极和高灵敏度应变片传感器同步记录结肠电-机械活动,即结肠运动、慢波和快波,并采用Ag-AgCl电极记录结肠体表电活动.信号由计算机系统软件采集并分析;放射性免疫方法测定SP,VIP;用免疫组织化学方法显示结肠组织内nNOS.结果脾虚组同正常组相比,结肠组织SP含量增高[(18.31±2.37)ng@g-1,(1.45±0.43)ng@g-1,P<0.05],VIP含量降低[(3.43±1.12)ng@g-1,(6.48±2.56)ng@g-1,P<0.05],结肠肌层中nNOS阳性神经细胞和神经纤维增多,运动频率降低[(3.6±1.1)min-1,(5.8±2.6)min-1,P<0.05].加味四君子汤治疗后各指标基本恢复正常.应激组同正常组相比,SP含量增高[(28.41±11.56)ng@g-1,P<0.05],运动振幅增高(1.6g±0.6g,0.9g±0.4g,P<0.05),体表结肠电活动与慢波的相关性比较,脾虚组和应激组均低于正常组(P<0.05)结论①脾虚状态下结肠SP、VIP含量及nNOS发生改变,结肠动力紊乱,但体内仍存在调节稳态的机制;nNOS升高VIP则降低.②加味四君子汤对脾虚结肠动力紊乱有一定调理作用.③冷束缚应激时SP升高,结肠动力紊乱以振幅升高为主.④体表结肠电活动与慢波的峰值频率相关性在各组间发生的变化,提示脾虚和冷应激皆为包括肌肉和神经系统在内的全身病变,对体表电活动产生影响.     

肠易激综合征患者的动力紊乱

1995年12月欧洲肠易激综合征(IBS)研究协作组在柏林召开了第七届IBS专题研讨会,主要内容如下。 (1)IBS患者胃肠动力型式:小肠测压证实,IBS患者消化间期移行性运动复合波(MMC)次数增加,间期缩短,胃肠动力指数增高,而MMCⅡ相延长,偶而自回肠至结肠有向下传播的巨大收缩波。该向下传播的收缩与腹痛有明确关系见于61%IBS患者,而在对照组     

血红素氧合酶的干预对糖尿病大鼠结肠动力障碍的影响

目的:探讨血红素氧合酶(heme oxygenase,HO)的干预对糖尿病(diabetes mellitus,DM)大鼠结肠动力障碍的影响.方法:链脲佐菌素ip建立DM模型,饲养6 wk时以碳沫推进实验证实DM大鼠存在胃肠慢传输运动后,所有大鼠分为正常对照组、DM未干预组、DM Hemin组[予HO诱导剂正铁血红素(Hemin)]及DM ZnPP组[予HO阻滞剂锌原卟啉(zinc protoporphyrin Ⅸ,ZnPP Ⅸ)];监测体质量、血糖.饲养9 wk时再测胃肠推进率,离体肌条实验记录结肠平滑肌条自发收缩反应及对Ach的反应性,Western blot及免疫组化检测近、远端结肠HO的表达.结果:6 wk时DM大鼠胃肠慢传输运动模型建立.HO干预对DM大鼠体质量、血糖无影响(P＞0.05).9 wk时Western blot示DM未干预组(1.20±0.09)、DM Hemin组(1.08±0.11)及DM ZnPP组(1.10±0.08)近端结肠HO-2表达无显著差异(P＞0.05),但均较正常对照组(1.66±0.14)显著减少(P＜0.05);各实验组远端结肠HO-2表达无差异.正常对照组与DM未干预组近、远端结肠HO-1的表达无差异(Western blot示HO-1/α-tubulin:近端结肠0.22±0.02 vs 0.22±0.03;远端结肠0.23±0.03 vs 0.23±0.03,P＞0.05);DM Hemin组结肠HO-1的表达(近端结肠0.66±0.09;远端结肠0.47±0.07)较前两组显著增多(P＜0.05);DM ZnPP组结肠HO-1基本无表达.DM Hemin组胃肠推进指数(54.4%±2.9% vs 63.0%±1.2%,P＜0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组显著下降(P＜0.05),而DM ZnPP组胃肠推进指数(72.5%±2.6% vs 63.0%±1.2%,P＜0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组明显改善(P＜0.05).结论:HO干预(诱导或阻断),对DM大鼠体质量、血糖无影响.诱导HO-1使DM大鼠慢传输型结肠动力障碍加重,而阻断HO-1可能改善DM大鼠慢传输型结肠动力障碍.     

内吗啡肽对泻剂结肠大鼠结肠肌电活动的影响

目的研究内吗啡肽对泻剂结肠大鼠结肠肌电活动的影响,探讨慢传输性便秘的发病机制。方法建立泻剂结肠动物模型,测定内吗啡肽1和内吗啡肽2对大鼠结肠肌电活动的影响。结果泻剂组大鼠结肠慢波频率和振幅分别为(28.19±7.51)次/min和(0.076±0.018)mV,与对照组比较[(36.05±8.94次/min)和(0.600±0.310)mV]明显降低;内吗啡肽1、内吗啡肽2以浓度依赖方式抑制泻剂结肠的慢波肌电活动,振幅明显降低,频率[(2 8.18±7.51)次/min3无明显变化,内吗啡肽1的作用强于内吗啡肽2。注射内吗啡肽不能阻断乙酰胆碱对结肠的兴奋作用。阿片受体拮抗剂纳洛酮(naloxone)能逆转内吗啡肽的抑制作用。结论内吗啡肽参与了泻剂结肠大鼠结肠肌电活动和结肠动力的调控,可能是慢传输性便秘发病的重要因素之一。     

白萝卜提取物对实验动物胃肠动力的促进作用及其可能的机制

目的探讨白萝卜提取物（Raphanus sativus roots extract,Rex）对实验动物胃肠运动的影响并探讨其可能的作用机制。方法灌胃给药（剂量10、30、100 mg/kg）后,测定小鼠胃内容物的残留率、小肠中阿拉伯胶活性炭粉混合物的推进距离;制作豚鼠回肠离体肠段标本,测定给药前后肠段平滑肌收缩强度和频率的变化情况;多导生理记录仪检测大鼠胃及十二指肠电活动;放射免疫法测定大鼠血浆胃动素含量变化。结果与阴性对照组相比,白萝卜提物在10-100 mg/kg时可使胃残留率明显减少,小肠推进百分比明显增加;并剂量依赖性地使离体豚鼠回肠平滑肌收缩;大鼠胃及十二指肠电活动的慢波频率和振幅明显增加,血浆胃动素水平明显升高（P〈0.05或P〈0.01）。结论白萝卜提取物可明显促进实验动物胃肠运动,该作用的发挥可能与胃动素水平升高及促进胃十二指肠电活动有关。     

Peptidergic nerves in the colon of patients with ulcerative colitis

BACKGROUND/AIMS: The cause of impaired motility, such as diarrhea and toxic megacolon, in patients with ulcerative colitis is unknown. Neuropeptides have recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiological significance of vasoactive intestinal polypeptide, substance P and neurotensin in the colon of patients with ulcerative colitis, we investigated the enteric nerve responses on lesional and normal bowel segments derived from patients with ulcerative colitis and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-four specimens were obtained from the lesional colon of 6 patients with ulcerative colitis (4 male, 2 female; ages 14-51 years, mean: 40.3 years). The patients with ulcerative colitis had chronic disease (4 with moderate disease, 2 with severe disease). Seventy-two specimens were obtained from the normal colon of 10 patients with colonic cancer (8 men and 2 women; ages 40-56 years, mean: 51.2 years). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: (1) Peptidergic nerves such as vasoactive intestinal polypeptide, substance P, and neurotensin nerves were found to act on both normal colon and ulcerative colitis colon; (2) the colon with ulcerative colitis was more strongly innervated by vasoactive intestinal polypeptide nerves than the normal colon; (3) Substance P and neurotensin nerves act more weakly in the UC colon that the normal colon. CONCLUSIONS: These findings suggest that peptidergic nerves play an important role in the impaired motility observed in patients with UC.     

Spontaneous contractions and some electrophysiologic properties of circular muscle from normal sigmoid colon and ulcerative colitis

Spontaneous contractions, inhibitory responses produced by electrical field stimulation, and some electrophysiologic properties of circular smooth muscle from normal sigmoid colon and from sigmoid colon of ulcerative colitis patients were compared in vitro using simultaneous recordings of mechanical and intracellular electrical activity. In normal colonic circular muscle obtained from 21 patients, the frequency of spontaneous summation contractions ranged from 3 to 7 per 4 min, whereas in circular muscle from 13 patients with ulcerative colitis, the frequency of these contractions ranged from 1 to 9 per 4 min. Nonadrenergic, noncholinergic relaxation produced by electrical field stimulation was recorded in the majority of circular smooth muscle strips from both normal colon and colon from patients with ulcerative colitis. There were no significant differences in mean resting membrane potential, mean slow-wave frequency, mean maximum slow-wave amplitude, or inhibitory-junction potential amplitudes recorded using circular smooth muscle from both normal colon and colon from patients with ulcerative colitis. There appeared to be a weak association in patients with ulcerative colitis between increasing duration of symptoms and decreasing frequency of spontaneous summation contractions, but there were no associations between the frequency of these contractions and the severity of colonic inflammation, patient age, or the frequency of stools. The mechanism accounting for a wider range in the frequency of summation contractions recorded from colonic circular smooth muscle in ulcerative colitis remains to be determined.     

Mobilization of tissue kallikrein in inflammatory disease of the colon

Colonic tissue was taken at operation from 10 patients with active ulcerative colitis and three patients with uncomplicated diverticular disease but with severe symptoms. Levels of kininogen, kallikrein, and kallikrein precursor were measured in blood-free tissue samples. In normal colon tissue a kininogen occurred in the muscle and none was detected in the mucosa. Kallikrein and its precursor were found in mucosa but not in muscle. In acutely inflamed tissue from ulcerative colitis patients relatively high levels of active kallikrein were detected in the underlying colonic muscle. There was little change in the level of kallikrein in inflamed mucosa or of kininogen in the muscle of these patients. No kallikrein was found in colonic muscle from patients with diverticular disease and the mucosal kallikrein level in these patients was unchanged. The findings suggest a mechanism for the formation of kinins in the wall of the colon which is present in ulcerative colitis but not in diverticular disease.     

Altered expression of mucins throughout the colon in ulcerative colitis.

BACKGROUND/AIMS: Regional differences in the biology of the colonic epithelium may determine the extent of involvement by ulcerative colitis. Novel monoclonal antibodies (MAbs) were used in this study to investigate regional heterogeneity in the colonic mucosa. METHODS: MAbs generated using a method of tolerisation against common antigens in the proximal colon and distal colon were used for immunoperoxidase staining, comparative histochemistry, immunoblotting, and slot-blot analysis. RESULTS: The colon specific MAbs 5F1 (IgG3) and 6G4 (IgM) stained goblet cell contents throughout the normal distal colon but staining was markedly reduced in the proximal colon (p < 0.0001). In the distal colon of patients with ulcerative colitis, whether quiescent or actively inflamed, reactivity was reduced compared with controls (p < 0.05, p < 0.001 respectively). By contrast, an overall increase in staining was seen in the uninflamed proximal colon in ulcerative colitis compared with controls (p < 0.02). Comparative staining with high iron diamine and biochemical analyses indicated that MAb 6G4 was reactive with mucin bearing sulphate or O-acetylated sialic acid groups, or both. CONCLUSIONS: Regional differences in the staining characteristics of normal colonic mucin have been shown using novel monoclonal antibodies. The pattern of mucin expression throughout the colon in ulcerative colitis is altered even in the absence of histological changes.     

高迁移率族蛋白B1抗体对结肠炎小鼠结肠黏膜的保护作用

背景:我国溃疡性结肠炎(UC)发病率明显上升,但目前尚无满意的治疗方法,因此研究其发病机制并寻求新的治疗途径具有重要意义。目的:研究高迁移率族蛋白B1(HMGB1)抗体对结肠炎小鼠结肠黏膜的影响。方法:36只BALB/c小鼠随机分为正常对照组、结肠炎模型组和HMGB1抗体治疗组,后两组以3%葡聚糖硫酸钠(DSS)制备小鼠结肠炎模型,HMGB1抗体治疗组小鼠腹腔注射HMGB1抗体。实验第7d,处死小鼠。行结肠组织学评分,测定结肠通透性,分别以RT-PCR和蛋白质印迹法检测结肠组织HMGB1 mRNA和蛋白表达。结果:与正常对照组相比,结肠炎模型组小鼠结肠组织学评分、结肠通透性以及HMGB1 mRNA和蛋白表达显著增高(P0.05)。与结肠炎模型组相比,HMGB1抗体治疗组小鼠结肠组织学评分、结肠通透性和HMGB1蛋白表达显著降低(P0.05)。结论:HMGB1参与了结肠炎小鼠的炎症反应过程,HMGB1抗体可有效抑制结肠炎小鼠结肠组织HMGB1表达,改善肠黏膜屏障功能,从而对UC结肠黏膜损伤起有明显保护作用。     

Total Antioxidant Capacity of Colon in Patients with Chronic Ulcerative Colitis

It has been proposed that oxidative stress is involved in the pathophysiology of ulcerative colitis. We have reported the depletion of the nonenzymatic antioxidant, glutathione, in colon from active and inactive ulcerative colitis. The colon contains several biochemically linked antioxidant systems. We hypothesized that diminished total antioxidant capacity in active ulcerative colitis would be associated with increased colonic lipid peroxidation. This study was designed to determine total antioxidant capacity and lipid hydroperoxide levels using colon obtained at surgery from controls (N = 16; 4 females, 12 males; mean age 70 years), and active and inactive ulcerative colitis (N = 15; 3 females, 12 males; mean age 39). Total antioxidant capacity of control colon was higher in muscularis externa compared to the mucosal–submucosal layer (P < 0.05). There were no differences in colonic total antioxidant capacity or lipid hydroperoxide levels comparing control colon to inactive and active ulcerative colitis. The results did not support depletion of tissue total antioxidant capacity by free radicals. Depletion of glutathione in ulcerative colitis may be a specific disorder rather than a secondary defect attributable to global oxidative stress. Nonspecific antioxidant supplements appear unlikely to be beneficial in the treatment of ulcerative colitis.     

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.     

Clinical application of computed tomography virtual colography

OBJECTIVE : To investigate the computed tomography (CT) virtual colographic features of colonic polyps, colorectal cancer, diverticula, ulcerative colitis and other benign colonic lesions. Also, to assess the value of this method in the diagnosis of colorectal lesions. METHODS : Computed tomography colography was performed in 37 patients (26 male, 11 female) suffering from the following conditions: 20 colonic adenomas, six colon cancers, four diverticula, five ulcerative colitis and one each of melanosis coli and amyloidosis. The data from CT scanning were processed by computer with specific software and the colonic lesions were evaluated with 2‐ or 3‐D images, depending on the individual software. RESULTS : Seventeen cases of colonic adenoma, six colon cancers, four diverticula and two cases of ulcerative colitis were detected by using CT colography. However, melanosis coli and amyloidosis of the colon were not detected. CONCLUSION : Computed tomography colography can detect all colonic polyps of 0.5 cm in diameter or larger, colon cancer, diverticula and some ulcerative colitis successfully. It is quick, minimally invasive and able to be tolerated well. It has the potential to become an effective radiological tool in diagnosing colonic lesions.     

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 < 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 < 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 < 0.05). These results suggest that colonic inflammation in ulcerative colitis is associated with alterations in cellular PTK activity.     

Detection of colonic antigen(s) in tissues from ulcerative colitis using purified colitis colon tissue-bound IgG (CCA-IgG)

In our report of a disease-specific colonic tissue-bound antibody (CCA) from patients with ulcerative colitis (Proc Natl Acad Sci USA 1978;75:4528), crude CCA was largely fragmented, and the yield was small. We have modified the extraction procedure to increase the yield of intact IgG present in CCA by sequential elution, storage of tissues in presence of a protease inhibitor, 2 mM Phenylmethylsulfonyl Fluoride, and use of Phenylmethylsulfonyl Fluoride in extraction buffers. Intact CCA-IgG was purified using protein A-Sepharose 4B affinity chromatography. 125I-CCA-IgG formed immune complexes in vitro with the aqueous extracts of colonic mucosa from 5 patients with ulcerative colitis but not from 6 patients with Crohn's disease and 6 normal colons from patients with carcinoma (p less than 0.01). We also performed reverse experiments by iodination of the colonic mucosal extracts with Bolton-Hunter reagent and incubating them with several preparations of CCA-IgG. Mucosal extracts of colon from 3 patients with ulcerative colitis bound significantly with CCA-IgG when compared with the identical extracts from 3 patients with Crohn's disease, 3 with a normal colon (p less than 0.005), and with the control human IgG (p less than 0.025). These studies demonstrate a better method of extraction and purification of intact CCA-IgG. Intact CCA-IgG binds to a specific protein(s) present in the homogenates of colonic mucosa from patients with ulcerative colitis but not from patients with Crohn's disease and normal colon.