调中颗粒对混合反流性食管炎大鼠的疗效

目的:研究调中颗粒对混合反流性食管炎大鼠食管黏膜血管活性肠肽(VIP)、P物质(SP)的水平及血浆中脂质过氧化物(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性的影响.方法:将大鼠随机分成5组,调中颗粒组(A组)、西沙必利组(B组)、半夏泻心汤组(C组)、正常对照组(D组)、空白模型组(E组),用食管十二指肠端侧吻合术法制备混合反流性食管炎大鼠模型,于给药2wk处死大鼠,HE染色观察病理改变,免疫组织化学技术检测大鼠胃黏膜VIP和SP的水平,比色法检测血浆中SOD、MDA和GSH-PX的活性.结果:与E组比较,A、B、C组光镜下食管黏膜组织有不同程度的修复,平均R值分别为0.8532、0.5521、0.7865,差异显著(P＜0.05),其VIP和SP表达明显增强(VIP:11 3.61±11.36、118.74±12.81、107.33±15.95vs91.05±10.66,P＜0.05:SP:132.24±10.5l,140.86±11.63,133.54±14.02vs113.73±16.37,P＜0.05);MDA含量降低(4.11±0.37,4.64±0.60,4.29±0.29vs5.77±0.16,P＜0.051、SOD和GSH-PX的活性提高(SOD:431.94±21.87,402.98±36.59.384.66±46.02 vs 345.02 ±24.11,P＜0.05:GSH-PX:135.83±3.71,118.26±6.34,122.78±4.76vs112.77±6.20,P＜0.05.结论:调中颗粒可能通过SP和VIP表达增强来调节胃肠运动从而降低MDA的含量,提高SOD和GSH.Px的活性,抑制反流性食管炎的发展,促进黏膜的修复,从而起到抑制胃肠内容物的反流和反流性食管炎的发展的作用.     

加味四逆泻心汤对慢性萎缩性胃炎大鼠血清促胃液素及血浆胃动素水平的影响

[目的]观察加味四逆泻心汤对慢性萎缩性胃炎(CAG)模型大鼠血清促胃液素(GAS)及血浆胃动素(MOT)水平的影响,探讨其作用机制。[方法]SD大鼠56只,随机抽取12只为空白(A)组;其余44只用2%水杨酸钠和30%乙醇的混合溶液灌胃,大鼠日常饮用0.1%氨水、并结合饥饱失常等因素,造成CAG模型后,随机分为模型(B)组,维酶素(C)组,加味四逆泻心汤(D)组。分别给予0.85%氯化钠、维酶素、加味四逆泻心汤灌胃。4周后处死动物,检测血清GAS、血浆MOT水平,光镜观察胃黏膜病理学改变。[结果]D组血清GAS水平较B组明显升高(Р<0.01);血浆MOT水平较B、C组明显降低(Р<0.05)。[结论]加味四逆泻心汤能明显改善CAG模型大鼠的一般状况,并使异常的GAS和MOT水平向正常恢复,提示该方可能是通过对胃肠激素水平的影响而达到有效治疗CAG的目的。     

调中颗粒对胃肌间Cajal间质细胞功能及数量的影响

[目的]观察功能性消化不良（FD）大鼠胃肌间Cajal间质细胞（ICC）超微形态结构、分布特点和密度变化,探讨调中颗粒治疗FD的机制。[方法]将40只大鼠随机分为5组,各8只,除正常组外,其余采用夹尾法制备FD模型,胃电图的方法检测造模是否成功,电镜观察胃肌间ICC的超微结构。酪氨酸激酶受体c-kit免疫组化法观察不同药物治疗后胃肌间阳性ICC的分布和水平变化。[结果]模型组大鼠胃电参数低于正常组（P〈0．05）;ICC的超微结构证实ICC与胃平滑肌运动具有密切相关性;调中颗粒能明显升高胃窦ICC水平（P〈0．05）,优于多潘立酮（P〈0．05）。[结论]调中颗粒能通过调节ICC的分布和数量,升高胃窦ICC的表达,促进胃蠕动,改善FD大鼠胃电节律。调中颗粒疗效优于半夏泻心汤和多潘立酮,具有整体调节作用。     

疏肝活血健脾方对门脉高压性胃病大鼠胃肠激素的影响及防治作用

[目的]从胃肠激素水平,研究疏肝活血健脾方对门脉高压性胃病(PHG)的防治作用。[方法]选择健康雄性Wistar大鼠120只,随机分为8组,采用一期门静脉缩窄法制备PHG动物模型。按要求造模灌胃后,在预定时间采胃组织,用免疫组织化学技术图像分析法检测胃底组织促胃液素(GAS)、血管活性肠肽(VIP)水平。[结果]A组大鼠胃底组织GAS、VIP免疫组化平均灰度值较F组升高(P<0.01);B、C、D组大鼠胃底组织GAS、VIP免疫组化平均灰度值较E组升高(P<0.01),B组疗效优于D组(P<0.05)。[结论]GAS、VIP在PHG的发病机制中起着重要作用。疏肝活血健脾方对PHG的防治效果肯定。     

中药泻心汤对大鼠胃排空和胃肠激素的影响

目的:观察半夏泻心汤(BX)、生姜泻心汤(SJ)和甘草泻心汤(GC)对大鼠胃排空及胃肠激素的影响.方法:60只SD大鼠随机分为正常对照组(n=15)、半夏泻心汤组(n=15)、生姜泻心汤组(n=15)和甘草泻心汤组(n=15),大鼠连续灌胃7d,半夏、生姜和甘草泻心汤组给药量分别为5.67,7.42,5.36g/(kg?d);通过测定大鼠胃内标记物-葡聚糖蓝的相对残留率来观察胃排空能力;采用放射免疫学的方法测定大鼠血中胃肠激素的含量。结果:与正常对照组(99.9%±32.2%)相比,半夏泻心汤组(66.1%±21.1%,P=0.014)胃内色素相对残留率明显减少,生姜泻心汤组(141.8%±21.07%,P=0.012)胃内色素相对残留率明显增加,甘草泻心汤胃排空作用不明显.与正常对照组相比,半夏泻心汤组的血管活性肠肽(VIP)、P物质(SP)水平下降显著(348.1±102.5ng/Lvs445.8±101.9ng/L,P=0.032;47.0±15.2ng/Lvs63.0±14.7ng/L,P=0.011);半夏、生姜泻心汤组生长激素(SS)水平明显升高(562.3±149.7,553.9±98.9ng/Lvs461.7±77.0ng/L,P=0.014和P=0.023);生姜、甘草泻心汤组胃泌素(GAS)水平(70.7±11.9,79.7±9.3ng/Lvs56.0±11.5ng/L,P=0.011和P=0.001)、胃动素(MTL)水平(205.0±22.0,205.1±43.1ng/Lvs162.6±19.5ng/L,P=0.001和P=0.014)显著升高.结论:三泻心汤对大鼠胃排空及胃肠激素的影响存在差异,可能是三方功能主治差异的原因之一.     

半夏泻心汤对PLGC大鼠胃黏膜组织病理学及HP的影响研究

[目的]通过观察大鼠黏膜外观、测定大鼠幽门螺旋杆菌(HP)、胃黏膜组织病理学指标,揭示半夏泻心汤对PLGC大鼠的影响及防治作用机制。[方法]130只清洁级雄性SD大鼠,采用改良MNNG+复合法造模PLGC大鼠110只,分组:模型组:PLGC大鼠100只;模型中药组:造模同时中药干预10只;空白组:正常喂养20只。中药干预阶段,剩余模型大鼠随机分为模型对照组10只、半夏泻心汤高、中、低剂量组分别为12、12、10只。观察检测各组大鼠黏膜外观形态、病理组织学及HP感染情况。[结果]中药干预后,大鼠一般情况及胃黏膜外观情况好转,高、中剂量组较为明显;病理组织学:模型中药组比模型组萎缩、肠化、异型增生率及HP感染率均较低,高剂量组、中剂量组比模型对照组萎缩、肠化、异型增生率及HP感染率均减低,高剂量组明显。[结论]中药半夏泻心汤对PLGC大鼠一般情况具有明显改善,黏膜病理具有逆转作用,对HP感染具有抑制作用。     

复方白及糊对反流性食管炎模型大鼠黏膜血流的影响

[目的]探讨复方白及糊治疗反流性食管炎（RE）的作用机制。[方法]实验大鼠随机分为4组,各23只。甲、乙、丙3组均采用改良部分贲门肌切开加外置幽门部分结扎术,制备RE大鼠模型,并与假手术组对照。甲组造模前7天起,每天灌食复方白及糊3ml;造模后与乙组一起每天灌食等量复方白及糊,丙组同时灌等量0.85%氯化钠。分别于术后7、14d观察各组大鼠食管下段pH值、大体标本及组织学改变,同时进行食管黏膜血流量的测定。[结果]造模成功,造模大鼠食管黏膜血流均有所下降,甲、乙组可使模型大鼠食管下段pH升高,损伤黏膜迅速修复,食管下端黏膜血流增加,其中甲组作用更强,与丙组、假手术组比较差异有统计学意义（P〈0.05）。[结论]复方白及糊治疗RE,可能是通过抑酸,改善局部黏膜血供,加强食管黏膜上皮屏障实现的。     

治萎防变胶囊对萎缩性胃炎大鼠胃黏膜NO/NOS和胃泌素、内皮素的影响

目的探讨治萎防变胶囊对慢性萎缩性胃炎(CAG)大鼠胃黏膜一氧化氮(NO)/一氧化氮合酶(NOS)和血清胃泌素(GAS)、血浆内皮素(ET-1)的影响。方法采用综合法成功复制CAG动物模型。施药治疗后分别对各组大鼠胃黏膜组织NO/NOS及GAS、ET-1含量进行检测。结果与空白组比较,模型组大鼠胃黏膜组织NO/NOS水平显著升高(P<0.01,P<0.05),血清GAS含量显著升高(P<0.05),血浆ET-1含量显著升高(P<0.05);与模型组比较,治萎防变胶囊可显著降低胃黏膜组织NO/NOS和血浆ET-1含量(P<0.05),显著提高血清GAS含量(P<0.05),且以治萎防变胶囊大剂量组作用显著。结论治萎防变胶囊具有提高机体抗氧化能力,减轻自由基损伤;降低血浆ET-1含量,促进血清GAS分泌,增加胃动力,改善胃黏膜血流量的作用。     

半夏泻心汤对化疗后呕吐家兔胃肠道反应的干预作用

目的探究半夏泻心汤对化疗后胃肠道反应的干预作用。方法采用顺铂(DDP)复制家兔化疗后胃肠道反应模型。随机分为模型组、半夏泻心汤组、恩丹司琼组,每组8只,观察3 w。结果 DDP所致家兔血浆P物质(SP)、血管活性肠肽(VIP)含量明显升高(P<0.05);半夏泻心汤组与恩丹司琼组SP、VIP含量明显降低(P<0.05)。结论半夏泻心汤可能通过对SP、VIP的调节抑制化疗后胃肠道反应。     

参七消痞颗粒对慢性萎缩性胃炎大鼠COX-2、Bcl-2的调节作用研究

[目的]观察参七消痞颗粒对慢性萎缩性胃炎(CAG)大鼠COX-2、Bcl-2蛋白表达的影响。[方法]通过N-甲基-N-硝基-N-亚硝基胍(MNNG)负荷其他因素建立CAG大鼠模型(14周),之后再随机分为模型组、摩罗丹组(阳性对照组1)、叶酸组(阳性对照组2)、参七消痞颗粒高、中、低剂量组,另从实验开始造模时就设立正常对照组(空白组)。各组大鼠给予相应药物灌胃治疗8周。治疗结束后,苏木精-伊红染色观察胃黏膜病理改变,ELISA法大鼠血清中PGI、PGII水平,并计算PGI/PGII;使用放射免疫法检测大鼠血清中GAS水平,免疫组织化学法检测大鼠胃组织COX-2、Bcl-2蛋白表达。[结果]与模型组比较,参七消痞颗粒中、低剂量组与模型组比较血清GAS水平显著降低(P0.01、P0.05),与空白组比较,模型组大鼠胃组织COX-2、Bcl-2蛋白表达均明显升高(P0.01),而参七消痞颗粒各剂量组及阳性对照组均较模型组降低(P0.01、P0.05)。[结论]参七消痞颗粒能明显改善CAG大鼠的胃黏膜病变,其治疗机制可能与下调COX-2、Bcl-2蛋白的表达有关。     

Esophagitis in sprague-dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.     

反流性食管炎时食管一氧化氮合酶表达的实验研究

目的：初步探讨反流性食管炎时食管ＮＯＳ的表达。方法：采用幽门半缝扎＋贲门肌切开术制备反流性食管炎动物模型,采用ＮＡＤＰＨ－ｄ组化染色观察食管ＮＯＳ表达,测定食管组织ＮＯ含量。结果：食管炎组大多呈ＮＯＳ强阳性反应,阳性率明显高于正常对照组（Ｐ＜０．００１）,食管组织ＮＯ含量也明显高于正常对照组（术后２４小时比较Ｐ＜０．０１,术后４８小时,７２小时比较均Ｐ＜０．０５）。结论：胃－食管反流可引起食管上皮粘膜ＮＯＳ的过度表达,过多的ＮＯ可能发挥着重要的作用。     

健胃冲剂对反流性食管炎模型大鼠血清胃泌素和胃动素分泌的影响

[目的]探索健胃冲剂治疗反流性食管炎(RE)的作用机制.[方法]采用“不全幽门结扎十贲门肌切开术”制作RE大鼠模型,将术后恢复较好的大鼠随机分为5组,即阳性对照组,西药对照组,中药高、中、低3个剂量组,同时设正常组,术后3周开始灌胃给药,连续给药3周后,腹主动脉取血,应用ELISA法检测各组大鼠血清胃泌素(GAS)和胃动素(MTL)的含量.[结果]中药高、中、低剂量组及西药对照组与阳性对照组相比,血清GAS及MTL含量均增高(P＜0.05),中药低剂量组对于提高MTL含量优于西药对照组(P＜0.05).[结论]健胃冲剂有助于调节GAS及MTL的分泌,使胃肠道运动功能增强,促进胃肠排空,减少胃内容物反流,也可提高食管下括约肌紧张性,增强廓清功能,从而对RE起到治疗作用.     

Protection effect of Xuanfudaizhetang on reflux esophagitis in rats

Objective:To study protection effect of Xuanfudaizhetang on reflux esophagitis in rats.Methods:A total of 50 Wistar rats were randomly divided into groups A,B,C,D and E with 10 in each.Reflux esophagitis model in rats was established by incomplete helicobacter seam+lower esophagus sphincterotomy.All rats were divided into 5 groups:group A as control group,group B as model group,group C with saline lavage treatment,group D with motilium treatment,group E with Xuanfudaizhetang lavage treatment.Recovery of esophageal,gastric mucosa and pH changes of rats were compared between groups.Results:Weight gain in group D and E was significantly higher in than group C;the esophageal mucosa grades and esophagus tissue pathological morphology grades of group D and E were higher than that of group B and C with significant difference between groups(P0.05);pH of lower esophageal mucosa in group D and E increased significantly than that in the group B and C(P0.05),and the distal mucosal pH dropped significantly in the group B and C(P0.05).Conclusions:Xuanfudaizhetang can obviously improve the pH of lower esophageal mucosa in rats with reflux esophagitis,decrease pH value of gastric mucosal,thus improve esophageal mucosa pathological conditions to achieve therapeutic effect on reflux esophagitis.     

旋覆代赭汤对酸性反流性食管炎模型大鼠食管下段粘膜pH值的影响

目的 :观察旋覆代赭汤对酸性反流性食管炎模型大鼠食管下段粘膜 p H值的影响。方法 :用不全幽门结扎加食管下括约肌 (L ES)切开术制备酸性反流性食管炎大鼠模型后 ,给予旋覆代赭汤水煎剂 ,分别于治疗 2、4、8d后观察各组大鼠食管下段粘膜 p H值的变化。结果 :用旋覆代赭汤治疗 4 d后 ,食管下段粘膜 p H值即有明显改善 ,与假手术对照组相比差异无显著性意义 (P >0 .0 5 )。结论 :旋覆代赭汤在治疗酸性反流性食管炎的过程中 ,通过抑制酸反流、抗炎等作用 ,明显提高食管下段粘膜的 p H值 ,从而促进疾病的恢复。     

Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.     

Ornithine decarboxylase (ODC) levels in children with reflux esophagitis

Reflux esophagitis is a common disease in infants and can be diagnosed largely by esophageal biopsy. In adults, chronic esophagitis may lead to Barrett's esophagus, a premalignant condition for esophageal cancer development. Ornithine decarboxylase (ODC) is used as an early marker for colon cancer development. No data are available on the role of ODC in reflux esophagitis in the pediatric population. In this study we retrospectively analyzed ODC activity in esophageal biopsies of children who underwent upper endoscopy. According to the esophageal histology, patients were divided into three groups: normal mucosa, mild, and moderate/severe esophagitis. None of our patients had esophageal metaplasia or cancer. ODC level was significantly higher in the moderate/severe esophagitis group compared to mild and normal mucosa group. We conclude that ODC activity is directly proportional to the severity of the esophageal inflammation/regenerative process in children with reflux esophagitis.     

Increased Taurine Content in Esophageal Mucosa of Children Affected by Gastroesophageal Reflux

We studied the possible involvement of mucosal amino acid metabolism in the pathogenesis of gastroesophageal reflux disease in children. Eighteen children with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without) and 10 children with normal 24-h esophageal pH monitoring as a comparative group underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa amino acids were assayed by liquid chromatography. In children affected by gastroesophageal reflux disease we found an increase of mucosal taurine (P < 0.01) and a decrease of serine (P < 0.01). No differences were noted between patients with and without esophagitis. Significant positive correlations (P < 0.001; r = 0.626) were found between mucosal taurine content and reflux index. Plasma amino acid concentrations did not show any significant differences among groups. Our results indicate that biochemical alterations precede the histological findings of inflammation, likely reflecting the adaptive response of the esophageal mucosa to the gastric contents exposure.     

胃及十二指肠液对食管粘膜损伤的实验研究

目的：通过动物实验,研究胃及十二指肠液反流对食管粘膜的损伤情况及其分别在胃食管反流病（ｇａｓｔｒｏｅｓｏｐｈａｇｅａｌ ｒｅｆｌｕｘ ｄｉｓｅａｓｅ,ＧＥＲＤ）发病中所占的地位。方法通过不同手术方式制作三种食管反流动物模型,分别为单纯胃液反流（Ｇ组）、单纯十二指肠内容物反流（Ｄ组）及十二指肠胃内容物混合反流（ＤＧ组）。于不同病程分批取得食管标本进行大体及光镜下形态学。结果各实验组出现程度不等的反流     

不同病理类型食管黏膜组织中PDCD4表达水平比较及意义

目的比较不同病理类型食管黏膜组织中程序性细胞死亡因子4（PDCD4）表达水平,并探讨其意义。方法88例经临床及内镜下诊断为反流性食管炎。病理活检结果为非肠上皮化生25例（A组）、肠上皮化生25例（B组）、低级别上皮内瘤变16例（C组）、高级别上皮内瘤变组12例（D组）、腺癌10例（E组）。另取25例消化不良患者的正常食管黏膜组织作为对照组（N组）。用免疫组化法检测A、B、C、D患者病灶或N组患者正常食管黏膜组织中PDCD4。结果 N组PDCD4表达量为10.623±0.202,其中强阳性25例、弱阳性0例、阴性0例;A组分别为10.569±0.128和24、1、0例;B组分别为9.423±0.025和23、2、0例;C组分别为6.051±0.233和10、6、0例;D组分别为0.902±0.201和0、0、12例;E组分别为0.723±0.224和0、0、10例。