5-羟色胺2A受体拮抗剂减轻糖尿病肾病的实验研究

目的 :研究 5 羟色胺2A(5 HT2A)受体拮抗剂 (酮色林 )对糖尿病肾病 (DN)病理损害的影响。　 方法 :对链脲佐菌素诱导糖尿病大鼠模型 ,给予酮色林 1mg/ (kg·d)分别治疗 4周和 19周 ,用免疫酶标法检测α SMA肾小球系膜细胞的表达 ,免疫荧光染色和激光扫描共聚焦显微镜定量分析系膜区基质胶原Ⅳ蛋白 ,计算机病理图像分析系统定量检测肾小球面积、系膜区面积 ,RT PCR半定量测定肾小球TGF - β1mRNA的表达。 　结果 :与糖尿病未治疗组相比 ,酮色林治疗组第 4周时肾小球系膜细胞α SMA表达显著降低 ,第 19周时肾小球面积、系膜区占肾小球面积的比值以及系膜区胶原Ⅳ的含量及肾小球TGF β1mRNA的表达显著低于未治疗组。　 结论 :酮色林能抑制系膜细胞的活化及过度合成胶原Ⅳ ,减轻糖尿病大鼠肾小球肥大和系膜区扩张 ,抑制TGF - β1过度表达 ,从而有效改善DN病理损害     

Sonographic evaluation of proximal gastric accommodation in patients with functional dyspepsia

AIM: To assess the value of ultrasonography (US) in evaluation of proximal gastric accommodation disorder in patients with functional dyspepsia (FD). METHODS: Between April 2011 and March 2012, 45 patients with FD and 27 healthy volunteers were enrolled in this study. Two-dimensional ultrasound (2DUS) and 3-dimensional ultrasound (3DUS) were performed sequentially to measure proximal gastric area (PGA), maximal proximal gastric diameter (MPGD), and proximal gastric volume (PGV). These values were measured separately in the two groups every other 5 min for a duration of 25 min after the beginning of ingestion of a test meal. Air pocket grading was done separately for images of 2DUS and blocks of 3DUS obtained at five scanning time points. RESULTS: Both PGA and PGV of patients were significantly smaller than healthy controls (P = 0.000 and 0.002, respectively). Comparing the two parameters between the groups at each time point, the differences were also statistically significant (P = 0.000-0.013), except at 10 min for the PGV (P = 0.077). However, no overall difference was found between the groups in the MPGD measurements (P = 0.114), though it was statistically significant at a 20-minute examination point (P = 0.026). A total of 360 sets or blocks of images were obtained for both 2DUS and 3DUS. For the images analyzed by 2DUS, none were excluded because of gastric gas, and 50 (13.9%) and 310 (86.1%) sets were determined as air pockets grades 1 and 2, respectively. For the images analyzed by 3DUS, 23 (6.4%) blocks were excluded from the measurement due to presence of a large fundus air pocket (grade 3); fifty (13.9%) and 287 (79.7%) blocks were also graded as 1 and 2, respectively. CONCLUSION: Measurement of both PGA and PGV by 2DUS and 3DUS could be useful for assessment of the proximal gastric accommodation.     

盐酸昂丹司琼口腔崩解片预防胃癌辅助同步放化疗所致恶心呕吐疗效观察

目的：评价盐酸昂丹司琼口腔崩解片预防胃癌辅助同步放化疗致恶心呕吐的疗效和安全性.方法：将接受辅助同步放化疗的52例胃癌患者分为实验组（盐酸昂丹司琼口腔崩解片组,26例）和对照组（甲氧氯普胺组,26例）,观察2组恶心呕吐的发生率、不良反应和生活质量.结果：实验组的总体恶心呕吐的发生率明显低于对照组（46.2％ vs 88.5％,P＜0.05）,其中实验组和对照组3～4级以上恶心呕吐的发生率分别为15.4％和34.6％（P＜0.05）.结论：盐酸昂丹司琼口腔崩解片预防胃癌放化疗所致恶心呕吐疗效确切,安全性良好.     

Assessment of proximal gastric accommodation in patients with functional dyspepsia

Impaired gastric accommodation is one of the most important etiologic factors in the pathophysiology of functional dyspepsia.Ultrasound is a potential alternative method to study changes in gastric volume as a reflection of gastric accommodation.Ultrasound is suitable for patients because it is a non-invasive,easily repeated and non-radioactive procedure,and a previous study has demonstrated the feasibility of 3-dimensional ultrasound in examining functional dyspepsia.The brief article by Fan et al demonstrated that both the proximal gastric area and volume,measured by 2-and 3-dimensional ultrasound respectively,were significantly smaller in patients with functional dyspepsia than in healthy controls.These results are very interesting,but we raise the relevant point that it should have been mandatory to study both changes in gastric volume and their relationship with upper gastrointestinal symptoms in functional dyspepsia.In fact,the relationship between cardinal symptoms and several pathophysiologic mechanisms in functional dyspepsia remains a matter of debate.Moreover,further evaluation of distal gastric volume that has been previously implicated in the origin of functional dyspeptic symptoms is advisable.Therefore,impaired gastric accommodation does not serve as a clear marker of the cardinal symptoms experienced by patients with functional dyspepsia in daily life.     

经皮穴位电刺激改善功能性消化不良患者症状和胃容受性的相关机制

目的:探索经皮穴位电刺激(TEAS)治疗功能性消化不良(FD)中餐后不适综合征(PDS)的疗效和机制。方法:采用双盲、随机、对照研究,前瞻性选择于浙江大学医学院附属邵逸夫医院就诊、满足罗马Ⅳ诊断标准中的18～70岁的PDS患者40例,患者知情同意后随机分入TEAS组和模拟TEAS组,分别接受经皮电针刺激足三里、内关穴和...     

5-HT及电刺激对胃节律紊乱模型新西兰白兔胃电活动的影响

目的:观察5-HT及电刺激对胃节律紊乱模型新西兰白兔胃电活动的影响.方法:对以胰高血糖素造模的新西兰白兔胃节律紊乱模型采用外周注射5-HT、胃起步点起搏,电刺激室旁核和中缝大核(P7)的方法,四导胃浆膜电信号同步记录,分析胃体、及胃窦部胃电信号的平均频率,相位差,负相位比率,波形对应率,幅度等指标,考察5-HT,及电刺...     

Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.     

Effect of 5-HT3 receptor over-expression on the discriminative stimulus effects of ethanol

BACKGROUND: Drug discrimination studies using selective antagonists and agonists have suggested that 5-HT3 receptors may modulate ethanol's discriminative stimulus effects. However, conflicting data between laboratories leaves the issue of 5-HT3 receptor involvement in ethanol's discriminative stimulus effects in question. The present study utilized transgenic mice that over-express 5-HT3 receptors in conjunction with traditional pharmacological techniques to examine the contribution of 5-HT3 receptors to ethanol's discriminative stimulus. METHODS: Ten 5-HT3 over-expressing (5-HT3 OE) and 18 B6SJL wild-type (WT) mice were trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk reinforced operant sessions. After training, ethanol substitution and response-rate suppression dose response curves were determined for ethanol, midazolam, dizocilpine, cocaine, mCPP, MD-354, YC-30 and MDL-72222. Antagonism tests combining ethanol with MDL-72222 and ondansetron were also conducted. RESULTS: The 5-HT3 OE and WT mice learned the ethanol discrimination in a comparable number of training sessions. Similar patterns of substitution were generated in both groups of mice for most test drugs. 5-HT3 OE mice were more sensitive to the rate suppressing effects of dizocilpine and MDL-72222 than were WT mice. Neither of the 5-HT3 antagonist tested significantly attenuated ethanol's discriminative stimulus effects in either 5-HT3 OE or WT mice. CONCLUSIONS: The results of the present study are consistent with a minimal role of 5-HT3 receptors in transducing ethanol's discriminative stimulus effects. Over-expression of 5-HT3 receptors does not alter the relative efficacy of GABAA positive modulators or NMDA antagonists for producing ethanol-like discriminative stimulus effects. However, 5-HT3 receptor over-expression does appear to modulate the response-rate altering effects of the uncompetitive NMDA antagonist, dizocilpine, and the 5-HT3 antagonist, MDL-72222.     

Functional 5-HT receptor subtypes in the isolated canine common carotid artery

Summary The vascular responses to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT, a selective 5-HT₁-like receptor agonist), alphamethyl-5-HT (-M-5-HT, a relatively selective 5-HT₂ receptor agonist), noradrenaline (NA), and KCl were examined in isolated, cannulated, and perfused canine common carotid arterial preparations. They caused strong vasoconstrictions. The rank order of vasoconstrictive potency was 5-HT > -M-5-HT NA > 5-CT >> KCl. The 5-HT-induced vasoconstriction was significantly depressed by methysergide (a 5-HT₁ and 5-HT₂ receptor antagonist), ketanserin (a selective 5-HT₂ receptor antagonist), and spiperone (a selective 5-HT₂ receptor antagonist). The 5-CT- and -M-5-HT-induced vasoconstrictions were also significantly inhibited by methysergide, spiperone, and ketanserin. The NA-induced vasoconstriction was readily inhibited by bunazosin (an -adrenoceptor antagonist) and ketanserin but not significantly inhibited by spiperone and methysergide. KCl has a weak potency for producing a vasoconstriction of the canine common carotid artery. A relatively large dose of diltiazem (a calcium channel blocker) did not modify 5-HT-induced vasoconstrictions. From these results, we conclude that (a) the canine common carotid artery contains abundant 5-HT receptors; (b) there are no functional 5-HT₁ receptors, but 5-HT₂ receptors are prominent; (c) 5-CT-induced vasoconstrictions might be due to activation of 5-HT₂ but not to 5-HT₁ receptors; (d) 5-HT-induced vasoconstriction might not involve -adrenoceptors; and (e) the vasoconstriction related to 5-HT in the common carotid artery is not significantly mediated via activation of calcium ion channels of smooth muscle cells, but may be induced by calcium ions from intracellular stores.     

Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms

Gastric and gallbladder emptying after a standard liquid meal were studied in 65 patients with early satiety, bloating, pain at the right hypochondrium or the epigastrium, nausea, and occasionally vomiting. Fifty normal subjects were studied as a control group. Gastric and gallbladder emptying were evaluated by means of real-time ultrasonography (RUS). Serial RUS scans were made after a 12-hr fast and every 15 min after a standard meal for 2 hr. Patients were considered to have delayed gastric emptying or hypokinetic gallbladder when gastric diameters and gallbladder volume evaluated 45 min after meal were 2sd above the corresponding mean values of the normal subject group. Fifteen patients (23%) were found with delayed gastric emptying and 20 (30.7%) a reduced gallbladder emptying. None of our patients showed delayed gastric emptying and hypokinetic gallbladder simultaneously. The 20 patients with reduced gallbladder emptying were included in a double-blind randomized, placebo controlled, change-over study with cisapride (10 mg three times a day) for 30 days. Cisapride treatment reversed the gallbladder hypomotility within the normal range while placebo did not change the response to meal. Symptom score improved significantly after cisapride and placebo. It is concluded that in dyspeptic patients with reduced gallbladder response to a meal, cisapride may be of help in improving the kinetic abnormality. Dyspeptic symptoms, however, do not seem to be corrected with the described gallbladder motor abnormality.Part of this study was presented at the 1990 Meeting of the American Gastroenterological Association in San Antonio, Texas, and published in abstract form in the May 1990 issue ofGastroenterology.     

针刺对功能性消化不良患者近端胃动力的影响

目的：观察针刺对功能性消化不良患者机械性胃扩张近端胃动力的影响．方法：功能性消化不良患者60例分为针灸组和对照组,分别进行等容机械性胃扩张．观察近端胃动力参数：最小牵张压(MDP),初始容积和压力,最大耐受容积、压力和顺应性(容积和压力的比值)．结果：两组最小牵张压无显著性差异(5．28±2．62mmHg vs 4．98±1．87mmHg,P＞0．05),针灸组的初始压力和容积(8．06±2．95mmHg vs 5．40±2．41mmHg,560．9±119．5mL vs 352．0±139．3mL),最大耐受压力和容积(13．25±2．23mmHg vs 9．82±1．9mmHg,810．7±119．62mL vs 504．1±159．6mL),顺应性(61．2±18．6mL/mmHg vs 51．4±17．8mL/mmHg)均显著高于对照组(P＜0．05)．结论：针灸可以显著提高功能性消化不良患者的近端胃动力,降低内脏敏感性．     

Effect of cisapride on gastric emptying in dyspeptic patients

The effect of the new gastrokinetic agent cisapride on gastric emptying was evaluated in 17 dyspeptic patients using the dual radionuclide technique. Eight patients with idiopathic dyspepsia and nine postsurgical dyspeptic patients were studied and compared to a control group. Gastric emptying of solids and liquids was determined after ingestion of a standardized meal using^99mTc-sulfur colloid scrambled eggs as the solid phase and [¹¹¹In]DTPA-labeled water as the liquid phase. Following a basal study and on a separate occasion, each patient received an intravenous bolus of 10 mg of cisapride after ingestion of the test meal; 10 of the patients were restudied after a two-week period of chronic oral administration of the drug (10 mg four times a day). Baseline gastric emptying of solids was significantly delayed in idiopathic and postsurgical patients; liquid emptying was only delayed in the postsurgical group. Intravenous and oral administration of cisapride significantly shortened gastric emptying in both groups. In all but one patient, the clinical improvement was confirmed by the test. Cisapride appears to be a good alternative to metoclopramide and domperiodone in the treatment of dyspeptic patients. The dual radionuclide technique appears to be a useful physiologic tool for evaluating and predicting the efficacy of a gastric prokinetic therapy in man.     

肥大细胞在胃感觉过敏患者胃黏膜中的改变

目的：了解国人功能性消化不良（FD）患者是否存在胃机械感觉过敏，对胃感觉过敏患者胃黏膜肥大细胞数量及脱颗粒情况进行研究，探讨肥大细胞在胃感觉过敏中的作用。方法：运用电子恒压器测定40例FD患者和15例正常人的胃感觉阈值。根据感知阈值将23例FD患者分为两组：感觉正常组（FD－N）和感觉过敏组（FD－H）。免疫组化方法染色肥大细胞，计数肥大细胞数；图像分析了解肥大细胞在扩张刺激前后平均吸光度值（A）的变化；电镜观察大细胞超微结构改变。结果：FD患者对胃机械扩张刺激的感知阈值，不适阀值，疼痛阈值均较正常人显著下降（P＜0．01，P＜0．01，P＜0．05），感觉过敏感患者近端胃黏膜肥大细胞数量明显多于FD－N组和对照组（P＜0．05）。刺激前后感觉过敏患者肥大细胞平均A值减少百分数较FD－N组和对照组明显增多（P＜0．05），电镜观察到肥大细胞与神经末梢关系密切，肥大细胞释放的颗粒有向神经末梢靠扰趋势。结论：部分FD患者存在胃机械感觉过敏；胃感觉过敏与胃黏膜肥大细胞数量增多，脱颗粒增加有关。     

5-HT1-receptor agonist sumatriptan modifies gastric size after 500 ml of water in dyspeptic patients and normal subjects

Sumatriptan, a 5-HT₁-receptor agonist has been shown to delay gastric emptying of liquids and solids in humans. However, no data are available of the effect of sumatriptan on gastric adaptation after distension with liquids and on symptoms induced by gastric distension. In 23 normal subjects and 30 dyspeptic patients with normal upper gastrointestinal endoscopy and real-time ultrasonography, the transverse gastric proximal and distal area and sagittal axis of the proximal stomach were determined by real-time ultrasonography and computed tomography after 500 ml of water. The area was determined by real-time ultrasonography and computed tomography twice at times 48 hr apart. Thirty minutes before real-time ultrasonography, placebo or sumatriptam were give subcutaneously in a double-blind fashion. Epigastric pain, bloating, heartburn, and nausea were also monitored through an intensity score from zero to 10 performed during the test. In six dyspeptic patients, the gastric distension was performed also with real-time ultrasonography and computed tomography after placebo and hyoscine butyl-bromide, a quaternary anticholinergic agent. Real-time ultrasonography and computed tomography demonstrated that after sumatriptan there is a reduction in proximal and distal transverse area and an increase in the sagittal axis of the proximal stomach. Hyoscine butyl-bromide increased all gastric measurements. Among the symptoms evaluated, only nausea was significantly reduced by sumatriptan (P < 0.01). Sumatriptan modifies gastric size, with a reduction in the transverse section and an increase of the sagittal axis of the proximal stomach and improves the nausea induced by gastric distension in dyspeptic patients.     

Effects of ondansetron in early- versus late-onset alcoholics: a prospective,open-label study

BACKGROUND: Early-onset alcoholics (EOAs) have a greater familial loading for alcoholism, more severe progression of the disorder, a greater severity of comorbid psychopathology, and a poorer response to treatment than late-onset alcoholics (LOAs). Ondansetron, a 5-hydroxytryptamine-3 antagonist, was found to be superior to placebo in the treatment of EOAs, but not of LOAs. This study compared the tolerability and potential efficacy of an oral solution of ondansetron in EOAs versus LOAs. METHODS: Forty outpatients with alcohol dependence (67.5% male; 87.5% European American; 20 EOAs; 20 LOAs) received an oral solution of ondansetron at a dosage of 4 microg/kg twice daily for 8 weeks, together with weekly relapse-prevention therapy. RESULTS: EOAs had a significantly greater decrease in drinks per day, drinks per drinking day, and alcohol-related problems than LOAs. Changes in the level of carbohydrate-deficient transferrin were consistent with changes in self-reported drinking behavior. CONCLUSIONS: An oral solution of ondansetron seems suitable for the treatment of alcohol dependence, yielding findings consistent with evidence from a placebo-controlled trial that ondansetron, at a dosage of 4 microg/kg twice daily, is of value in the treatment of EOAs.     

功能性消化不良患者胃固体排空功能与其临床症状关系的研究

目的研究功能性消化不良运动障碍亚型患者胃固体排空功能与其临床症状的关系.方法对有4周以上腹胀、恶心、食欲减退等症状的患者进行症状评分,症状总积分≥9分,早饱、上腹胀至少具备一项且≥2分者,行胃镜、B超等有关检查,排除器质性病变后诊断为功能性消化不良运动障碍亚型.确诊患者服用标准试餐加固体小钡条,餐后5h透视确定胃内钡条排空情况;同时所观察患者服用西沙必利每次5mg、每日3次治疗,并于治疗2周及4周末复查.结果功能性消化不良运动障碍亚型中67.5%的患者有胃排空异常,女性与男性无显著性差异(P>0.05).治疗前胃排空正常者的症状积分为10.00±1.41,,胃排空异常者为11.70±2.28,二者相比无明显差异(P>0.05);治疗2周及4周后,胃排空正常者的症状积分分别为4.90±2.45、2.10±1.19,胃排空异常者则分别为7.00±3.12、4.20±2.39,与治疗前相比二者的症状总积分均明显降低,而且前者比后者的症状积分更低(P<0.05).治疗前患者的症状积分虽与胃内钡潴留无明显相关(r=0.078,P>0.05),但治疗后二者却有一定的相关性(r=0.47,P<0.05).结论功能性消化不良患者有明显的胃排空延迟;胃排空延迟确与运动障碍样症状有关,但与症状的严重程度无关;西沙必利治疗可使所有患者的症状及部分患者的胃排空不同程度改善.     

人参调脾散对腹泻型肠易激综合征患者结肠黏膜5羟色胺3受体mRNA表达的影响

[目的]检测腹泻型肠易激综合征（IBS-D）患者结肠组织5羟色胺3受体mRNA（5-HT3RmRNA）的表达水平,探讨中药人参调脾散治疗IBS-D的作用机制。[方法]采用逆转录-聚合酶链式反应（RT-PCR）方法分析IBS-D患者治疗前后及正常人（对照组）乙状结肠黏膜5-HT3RmRNA表达水平的变化。[结果]mS-D患者治疗前5-HT3RmRNA表达水平较对照组显著增高,2组比较差异有统计学意义（P〈0．05）;经人参调脾散治疗后5-HT3RmRNA表达水平减低,与对照组比较差异无统计学意义（P〉O．05）;IBS-D患者治疗前后5-HT3RmRNA表达水平自身比较差异有统计学意义（P〈0．05）。[结论]人参调脾散能通过下调IBS-D患者结肠黏膜5-HT3RmRNA表达,降低5-HT3R活性,达到治疗IBS-D的作用。     

功能性消化不良患者肠嗜铬细胞数量及功能改变

目的探讨作为5-羟色胺(5-HT)重要来源的肠嗜铬细胞(EC细胞)在功能性消化不良(FD)患者胃黏膜中的改变。方法对15例健康志愿者和33例FD患者进行研究,免疫组化法染色并计数EC细胞。电镜观察EC细胞超微结构。结果FD患者近端胃黏膜EC细胞数显著高于对照组(12．5±2．1比8．3±1．4,t=2．353,P＜0．05)。FD患者EC细胞染色强度较对照组明显增强(3．72±0．42比2．61±0．57,t=2．078,P＜0．05)。随胃黏膜炎症程度的加重,EC细胞数量增加,染色强度增强。电子显微镜下EC细胞内高尔基体、线粒体及内质网较多,胞质内有特异性分泌颗粒。结论EC细胞可能参与FD发病,EC细胞数量与胃黏膜炎症程度有关。