刚地弓形虫排泄-分泌抗原鼻内免疫小鼠诱导的免疫应答

目的 观察刚地弓形虫排泄-分泌抗原（ESA）鼻内免疫小鼠后对不同黏膜部位和系统的免疫效应。方法 用Vero细胞培养刚地弓形虫,提取ESA抗原;将5—6周龄BALB／c小鼠随机分为6组,每组10只,实验组分别用培养5、7、9、11和14d提取的ESA20μg/只鼻内免疫小鼠2次,间隔为2周;对照组用无攻虫的细胞培养上清液滴鼻。观察小鼠健康和死亡情况,记录体重。在末次免疫后第3周处死小鼠,分别分离派伊尔结（PP）、脾淋巴细胞、肠上皮内淋巴细胞（IEL）、肠系膜淋巴结淋巴细胞（MLNL）,并加以计数。收集粪便和眶血样本,ELISA检测粪内sIgA水平及血清IgG特异抗体。结果 实验期间小鼠健康状况良好,对照组和实验组小鼠体重均不同程度增加;末次免疫后第3周,实验组粪便sIgA、血清IgG、PP细胞、脾淋巴细胞、MLNL、IEL的数量均高于对照组,14d组（P〈0．01）的抗体滴度和各淋巴细胞计数最高。结论 用刚地弓形虫速殖子与Vero细胞共培养5—14d提取的ESA鼻内免疫小鼠均可诱导黏膜及系统特异性的免疫应答,共培养第14天提取的ESA免疫效果优于其他时间组。     

不同剂量弓形虫ESA鼻内免疫小鼠诱导的粘膜及系统免疫应答

目的观察不同剂量弓形虫排泄一分泌抗原（excreted／secreted antigens，ESA）鼻内免疫小鼠诱导的粘膜及系统免疫应答，确定适宜免疫剂量。方法40只BALB／c小鼠，雌雄各半，随机分为5组，每组8只。分别用5、10、20和30μg ESA滴鼻免疫小鼠2次，间隔14d，对照组用20μl/只PBS滴鼻。于末次免疫后第14d，颈椎脱臼处死小鼠，ELISA法检测鼻咽冲洗液和小肠冲洗液sIgA、血清IgG抗体水平，分离并计数肠上皮内淋巴细胞（intest inalintraepithelial lymphocytes，iIEL）、肠系膜淋巴结淋巴细胞（mesenteric lymph node lymphocytes，MLNL）及脾淋巴细胞。结果实验期间，小鼠健康状况良好。随鼻内免疫ESA剂量的增加，特异性抗体水平不同程度的升高，MLNL、iIEL及脾淋巴细胞也显示不同程度的增生性应答。其中，30μg组小鼠血清IgG、脾淋巴细胞数量与10μg组、5μg组和PBS组比较，差异有统计学意义（P〈0．05或P〈0．01）；30μg组小肠冲洗液sIgA、鼻咽冲洗液sIgA、iIEL和MLNL数量，20μg组小肠冲洗液sIgA和MLNL数量与5／2g组及PBS组比较，差异有统计学意义（P〈0．05或P〈0．01）；20μg组血清IgG与PBS组比较差异有统计学意义（P〈0．05）。结论20μg和30μg ESA鼻内免疫能有效诱导粘膜及系统免疫应答。     

霍乱毒素联合弓形虫排泄-分泌抗原鼻内免疫小鼠诱导的GALT和NALT黏膜免疫应答

目的观察霍乱毒素(CT)联合弓形虫排泄-分泌抗原(ESA)鼻内免疫小鼠诱导的肠相关淋巴组织(GALT)和鼻相关淋巴组织(NALT)黏膜部位的免疫应答。方法将48只5~6周龄BABL/c小鼠随机均分为3组,分别用PBS、ESA和CT+ESA滴鼻免疫小鼠2次,间隔2周。末次免疫后14 d,处死小鼠,ELISA测定小鼠粪便和鼻咽冲洗液sIgA抗体水平;计数派伊尔淋巴集结(PP)、肠上皮淋巴细胞(IEL)、NALT和鼻通道(NC)淋巴细胞数,免疫细胞化学法检测CD4+、CD8+T细胞亚群水平。结果免疫后14 d,CT+ESA组小鼠鼻咽冲洗液和粪便sIgA水平显著高于ESA组和PBS组(P<0.01);CT+ESA和ESA组小鼠GALT部位的PP淋巴细胞显著增生,主要以CD4+T细胞为主;而IEL以CD8+T细胞增生为主,CD4+/CD8+比值降低(P<0.05)。CT+ESA NALT内淋巴细胞明显增生。CT+ESA组NC淋巴细胞显著升高(P<0.01),以CD4+T细胞增生为主。结论 CT佐剂联合ESA滴鼻免疫BALB/c小鼠可诱导GALT和NALT黏膜部位免疫应答。     

不同剂量霍乱毒素联合弓形虫ESA小鼠鼻内免疫的佐剂效应

目的观察不同剂量霍乱毒素(cholera toxin,CT)联合弓形虫排泄-分泌抗原(excreted-secreted antigens,ESA)滴鼻免疫小鼠的佐剂效应,探索CT作为鼻黏膜佐剂的适宜剂量。方法 5~6周龄BALB/c小鼠60只,随机分为5组,每组12只,分别以0、0.5、1.0、1.5或2.0μg CT联合ESA 20μg滴鼻免疫小鼠,间隔2周进行加强免疫,共2次。末次免疫后30 d,眼静脉丛采血并颈椎脱臼处死小鼠,用ELISA法检测血清IgG和粪便sIgA水平。分离脾、Peyer’s patch(PP)、肠系膜淋巴结(MLN)淋巴细胞。结果 1.5和2.0μg CT组小鼠健康状况下降、存活率降低。免疫后30 d,小鼠粪便sIgA水平随CT剂量的增加而升高,1.0、1.5和2.0μg CT组小鼠粪便sIgA水平显著高于无佐剂组(P0.05),3组间差异无统计学意义(P0.05)。CT联合ESA鼻内免疫小鼠后MLN、PP和脾淋巴细胞数显著高于无佐剂组(P0.05),并均呈现一定的剂量效应,但较高剂量组(1.0、1.5和2.0μg)之间差异无统计学意义(P0.05)。结论 1.0μg CT联合ESA鼻内免疫小鼠可诱导较高水平的黏膜和系统免疫应答,且对小鼠的健康无不良影响。     

重组人IL-2联合STAg鼻内免疫BALB/c小鼠诱导的免疫应答

目的观察重组人白细胞介素-2（rhuIL-2）联合弓形虫可溶性速殖子抗原（STAg）滴鼻免疫小鼠诱导的免疫应答,探讨rhuIL-2的佐剂效应及适宜剂量。方法5～6周龄BALB/c小鼠60只,随机分为6组,每组10只。实验组以STAg20μg或分别加rhuIL-2250、500、1000、2000 IU滴鼻免疫,抗原与佐剂溶于20μlPBS中,对照组以PBS滴鼻,免疫2次,间隔2周。末次免疫后30d,颈椎脱臼处死全部小鼠,ELISA法检测血清IgG和粪便sIgA水平;分离脾淋巴细胞、肠上皮内淋巴细胞（iIEL）,并计数。结果与PBS组相比,各佐剂组血清IgG水平都有增高,其中STAg＋500 IU IL-2组IgG水平增高最显著（P〈0.01）;STAg＋500 IU IL-2组和STAg＋1000 IU IL-2组粪便sIgA抗体水平显著高于PBS组和STAg组（P〈0.05）。联合IL-2佐剂免疫小鼠脾淋巴细胞和产生了增殖性应答,其中STAg＋500 IU IL-2组和STAg＋1000 IU IL-2组脾淋巴细胞数显著高于PBS组和STAg组（P〈0.05）;TAg＋500 IU IL-2组iIEL高于PBS组（P〈0.05）。结论rhuIL-2作为佐剂联合STAg鼻内免疫小鼠可有效诱导粘膜免疫、系统的细胞免疫和体液免疫应答;500 IU IL-2为鼻内免疫小鼠的适宜剂量。     

不同剂量STAg滴鼻免疫小鼠诱导的抗弓形虫感染作用

目的观察不同剂量可溶性速殖子抗原(soluble tachyzoite antigen,STAg)滴鼻免疫小鼠诱导抗弓形虫感染作用,确定STAg滴鼻免疫最佳剂量。方法BALB/c小鼠50只随机分为5组,实验组分别用5μg、10μg、20μg、30μg STAg/只滴鼻免疫小鼠2次,间隔2周,对照组用PBS滴鼻。末次免疫后第14d,用4×104个速殖子/只灌胃攻击全部小鼠,观察小鼠健康和死亡情况,记录体重。攻击后第30d检测粪便IgA和血清IgG,计数脾、脑组织内弓形虫速殖子,分离并计数小肠上皮内淋巴细胞(intraepithelial lymphocyte,IEL)。结果20μg和30μg组小鼠存活率高于5μg、10μg及对照组。攻虫后对照组小鼠体重逐渐降低,而5μg组,10μg组(P<0.05),20μg组(P<0.05)和30μg组(P<0.05)小鼠体重仍呈增高趋势。20μg和30μg组脾、脑组织内虫荷(速殖子数)显著低于5μg、10μg组和对照组(P<0.05),实验组粪便IgA,血清IgG及IEL数量高于对照组。结论不同剂量STAg滴鼻免疫小鼠均可诱导抗弓形虫感染,20μg或30μgSTAg滴鼻免疫可诱导更有效的抗弓形虫感染保护作用     

弓形虫复合黏膜疫苗鼻内免疫小鼠抵抗弓形虫感染作用的观察

目的 观察弓形虫复合黏膜疫苗鼻内免疫小鼠诱导的肠黏膜和系统免疫应答及其抗弓形虫感染作用。方法 BALB/c小鼠52只随机分为两组（每组26只），免疫组小鼠用弓形虫复合黏膜疫苗（每毫升含可溶性速殖子抗原1 mg， 霍乱毒素50 μg） 20 μl/只滴鼻免疫2次，间隔2周；对照组用等剂量PBS滴鼻。末次免疫后14 d，各组处死6只，摘眼球取血（0.5～1 ml）；取直肠内粪便（4～5粒），ELISA测定血清IgG和粪IgA抗体；分别计数脾组织、派伊尔集合淋巴结（PP）和肠上皮淋巴细胞（IEL），免疫细胞化学法检测各组织中CD4⁺、CD8⁺ T细胞亚群水平。用RH株弓形虫速殖子（4×10⁴个/只）灌胃攻击感染各组其余小鼠，30 d后颈椎脱位处死，计数肝、脑组织速殖子虫荷。 结果 免疫后14 d，免疫组小鼠血清IgG和粪IgA抗体水平（分别为0.224和0.371），显著高于对照组（分别为0.041和0.037）（P<0.05），脾、PP和IEL中T淋巴细胞与对照组相比明显增生（P<0.01），其中脾、PP中CD4⁺、CD8⁺ T淋巴细胞增殖显著（P<0.05），IEL中以CD8⁺ T细胞为主，增殖显著（P<0.01），CD4⁺/CD8⁺ 比值降低（P<0.05）。攻击后30 d，免疫组小鼠存活率（85.0%）显著高于对照组（45.0%）（P<0.05）。免疫组肝、脑组织速殖子数比对照组分别减少86.3%、86.7%，两组差异有统计学意义（P<0.05）。 结论 弓形虫复合黏膜疫苗鼻内免疫小鼠，能有效诱导黏膜和系统免疫应答，小鼠存活率显著提高，肝、脑组织虫荷显著降低。     

弓形虫排泄-分泌抗原和可溶性速殖子抗原免疫原性的观察

目的观察弓形虫速殖子排泄-分泌抗原（excreted/secreted antigen,ESA）和可溶性速殖子抗原（soluble tachyzoite antigen,STAg）鼻内免疫小鼠的免疫原性。方法BALB/c小鼠随机分为4组,分别用PBS 20μl/只、体外排泄-分泌抗原（excreted/secreted antigenin vitro,ESAv）、腹腔排泄-分泌抗原（excreted/secreted antigen in mice,ESAm）和STAg各20μg/只鼻内免疫2次,间隔14 d。分别于末次免疫后14 d和44 d每组处死8只小鼠,计数肠上皮内淋巴细胞（intestinal intraepithelial lymphocytes,iIEL）和脾淋巴细胞,ELISA法检测血清IgG和小肠冲洗液sIgA抗体水平。结果实验期间,ESAm组小鼠于二次免疫后状态欠佳,其他各组小鼠健康状况良好。末次免疫后14 d,各抗原组脾淋巴细胞及iIEL均增殖活跃,细胞数与PBS组比较,差异具统计学意义（P〈0.05或P〈0.01）;至免疫后44 d,两种ESA组脾淋巴细胞及iIEL数与PBS组比较差异具统计学意义（P〈0.05）。各抗原组血清IgG水平在免疫后14 d和44 d均明显增高,与PBS组比较差异有统计学意义（P〈0.05或P〈0.01）。免疫后14 d肠液sIgA水平ESAv、ES-Am和STAg组与PBS组比较差异有统计学意义（P〈0.05或P〈0.01）,ESAm和STAg组与ESAv组比较差异有统计学意义（P〈0.05或P〈0.01）,两种ESA组在免疫后44 d与PBS组比较差异仍具统计学意义（P〈0.05）。结论ESAv、ESAm和STAg鼻内免疫均可诱导粘膜及系统的细胞和体液免疫应答,有较强的免疫原性。但ESAm可能对机体有毒副作用,不适宜直接鼻内免疫。     

弓形虫复合粘膜疫苗滴鼻免疫小鼠诱导的Peyer''''s patches持续性细胞免疫应答

目的以可溶性速殖子抗原（soluble tachyzoite antigen，STAg）和霍乱毒素（choleratoxin，CT）佐剂制备的弓形虫复合粘膜疫苗滴鼻免疫小鼠，观察肠粘膜诱导部位Peyer’s patches（PP）的细胞免疫应答及持续时间，探讨其免疫机制。方法BALB／c小鼠96只，随机分为实验组和对照组，实验组以STAg（20μg／只）为抗原，CT（1／μg／只）为佐剂滴鼻免疫，对照组PBS滴鼻。滴鼻2次（间隔2周）后，每组6只小鼠分别于第1、2、3、4、6、8、10、12周处死。计数PP个数，制备PP淋巴细胞悬液，计数并涂片；免疫细胞化学法检测CD4^＋、CD8^＋T细胞亚群。结果实验期间两组小鼠PP数目均无明显变化；实验组免疫后PP淋巴细胞数量明显增生，第2周达高峰，第1、2、3周显著高于对照组（P〈0.05），其中以CD4^＋T细胞增生为主，第1周～第8周高于对照组（P〈0.01），CD8^＋T细胞第1周～第4周显著增高（P〈0.01），CD4^＋／CD8^＋比值无显著变化（P〉0．05）。结论弓形虫复合粘膜疫苗滴鼻免疫BALB／c小鼠可有效诱导肠PP部位持续性的免疫应答，从而激活肠粘膜效应部位淋巴细胞的抗弓形虫感染作用。     

可溶性弓形虫速殖子抗原联合蜂胶和IFN-γ鼻内免疫小鼠诱导的细胞免疫应答

目的比较蜂胶、IFN-γ佐剂以及两种佐剂混合鼻内免疫辅助STAg增强机体细胞免疫应答的水平,探讨两种佐剂联合应用的免疫效果。方法将5~6周龄雌性BALB/c小鼠60只随机分为4组:20μg STAg组,20μg STAg+40μg蜂胶组,20μg STAg+1 000 U IFN-γ组和20μg STAg+40μg蜂胶+1 000 U IFN-γ组。将抗原和佐剂溶于20μl PBS中,双侧鼻孔(10μl/鼻孔)滴鼻免疫。免疫2次,间隔14 d,末次免疫后第10 d用RH株弓形虫速殖子4×104个/只灌胃攻击。逐日观察小鼠存活情况。攻击后第43 d处死全部存活小鼠,免疫细胞化学(ICC)法检测小鼠PP结、IEL和脾T淋巴细胞亚群水平。结果与STAg组相比,各佐剂组小鼠T淋巴细胞亚群比例有升高的趋势,其中IFN-γ、蜂胶+IFN-γ佐剂组小鼠PP结CD4+、CD8+T淋巴细胞,IEL、脾CD8+T淋巴细胞数显著高于STAg组,CD4+/CD8+T淋巴细胞比值倒置。结论在抗弓形虫感染中,IFN-γ的佐剂作用优于蜂胶,有效激发机体细胞免疫应答,可用作鼻内免疫抗弓形虫感染的粘膜佐剂。IFN-γ+蜂胶佐剂鼻内免疫效果优于单独蜂胶、IFN-γ佐剂,应用联合佐剂是抗弓形虫感染免疫的一个新思路。     

Measurement of gastric and duodenal mucosal protein turnover in humans

Conventional measurement of mucosal turnover is based on labeling cellular DNA with [³H]thymidine, but because of the risk of genetic damage, this technique is not suitable for studies in normal human subjects. Consequently, we have measured mucosal protein turnover by a primed/continuous intravenous infusion of tracer quantities of [1¹⁴C]leucine and measured its incorporation into mucosal protein at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by standard endoscopic techniques from the distal duodenum and gastric antrum. In addition, duodenal villous height and width were measured by microscopic micrometric techniques in order to calculate villous growth rate. Results demonstrated a mucosal protein turnover of 57±5%/day in gastric antrum and 39±2%/day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6 days, respectively. Average duodenal villous height was 433±77 m, suggesting a villous growth rate of approximately 160 m/day. As our mucosal protein turnover rates are similar to epithelial turnover rates measured by cellular labeling techniques, our results support the intestinal proliferon theory that suggests all mucosal elements follow similar turnover characteristics. In conclusion, the technique should provide a practical alternative method of studying the effect of disease upon mucosal regeneration and repair.     

CHANGES IN MUCOSAL PHOSPHOLIPID‐RELATED PROTECTION IN SOME GASTRIC DISEASES

Background: Phospholipids play an important role in gastric mucosal protection. The purpose of the present study was to investigate changes in various phospholipids in the fundic and pyloric gland mucosae of patients with gastric mucosal disease. Methods: One hundred and five patients with superficial gastritis, duodenal ulcer, gastric ulcer or gastric cancer were studied. Patients underwent endoscopy to obtain biopsy specimens from both the fundic and pyloric gland mucosae. The phospholipid contents were measured by high performance liquid chromatography. Results: Total phospholipid level was significantly greater in the fundic gland mucosa than in the pyloric gland mucosa (P = 0.037), and the level in the fundic gland mucosa was high in all four gastric diseases studied. The difference was significant in patients with gastric ulcers (P = 0.0156). Total phospholipid levels were the highest in superficial gastritis, followed by duodenal ulcer, gastric ulcer and gastric cancer. In all four gastric diseases, phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) levels were high, while phosphatidylinositol, lysophosphatidylcholine, and sphingomyelin levels were low. The PE and PC levels were higher in the fundic gland mucosa than in the pyloric glandular mucosa, whereas the PS level was higher in the pyloric gland mucosa than in the fundic gland mucosa. Conclusions: The fundic gland mucosa has stronger phospholipid‐related protection than the pyloric gland mucosa, based on the levels of mucosal phospholipids. The main phospholipids for gastric mucosal protection are PC and PE (in the fundic gland mucosa) and PS (in the pyloric gland mucosa). Phospholipid‐related protection is strong in superficial gastritis and duodenal ulcer, but is reduced in the pyloric gland mucosa in patients with gastric ulcers, and in both gastric gland mucosae in patients with gastric cancer.     

Acute Gastric Mucosal Injury Caused by Ingestion of Chlorinated Fungicide

We encountered a patient with acute gastric mucosal injury caused by ingestion of a chlorinated fungicide. Approximately 15 h after the episode of ingestion, endoscopic views were compatible with the acute gastric mucosal lesion of severe degree throughout the stomach. At that time, endoscopic biopsy showed congestion in the epithelial layer of the mucosa, along with lymphocytic infiltration that had likely existed from the onset of the condition. On the third day, the mucosal lesion looked more serious with peculiar hemorrhagic folds, and biopsy revealed exfoliation of the epithelial surface and neutrophilic infiltration in the stroma of the epithelial layer. On the seventh day, endoscopic images showed persistence of the lesion, but biopsy demonstrated the development of regenerating epithelium along with a marked reduction in infiltration of neutrophils and edema in the stroma.     

肠黏膜屏障损伤与保护分子机制研究进展

介绍肠黏膜屏障损伤因素的分子机制,如内毒素及氧自由基、炎症介质和细胞因子如白细胞介素（interleukin）、肿瘤坏死因子-α（TNF-α）、核转录因子kappa B、TOLL样受体（TLRs）和NOD受体通路、高迁移率族蛋白B1、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）等。对肠黏膜屏障的保护分子机制如肠上皮紧密连接蛋白、白介素家族、其它保护性调控因子等作出介绍。     

Changes in serum and intestinal diamine oxidase (DAO) activity after proximal enterectomy in rats

To determine whether serum and mucosal DAO activity reflects quantitative changes in the small bowel mucosal mass, we have chosen an experimental model of mucosal hyperplasia which is known to occur in the rat after enterectomy. A 50% proximal enterectomy or a single transection was performed in 20 growing rats weighing 145–160 g. Ten days following surgery, we determined mucosal mass parameters (weight, protein, and DNA content), sucrase activity, and DAO activity in the duodenum (segment A), proximal ileum (segment B), and distal ileum (segment C) of the remaining small intestine. Mucosal hyperplasia was demonstrated by the finding that in each segment, mucosal weight, protein, and DNA content per centimeter of gut length were significantly (P<0.01) higher (+38 to+78%) in the resected group than in transected controls. In segments B and C of resected rats, the changes in DAO activity expressed per gram of mucosa paralleled the changes in mucosal mass, the activity being increased by +69% and +49% (P<0.05) compared to the values recorded in transected controls. Expressed per centimeter of gut length, total DAO activity was also enhanced by +141% in segment B (P<0.05 vs controls) and by +87% in segment C(P>0.01 vs controls) of resected rats. In the duodenum, the changes in DAO activity were small (+36%) and not significant. In the ileum (segment C), significant correlations were established between total DAO activity and either mucosal weight (r=0.75,N=20,P<0.01) or mucosal DNA concentration (r=0.78, N=20, P<0.01) per centimeter of gut length, but there was no correlation between DAO activity and sucrase activity. Compared to control rats with transection, proximal enterectomy produced marked changes in the serum activity of DAO. Ten days following surgery, the mean value of serum DAO was fivefold higher (P< it0.005) in the resected group than in the transected group. These data indicate that after jejunectomy (1) the intestinal activity of DAO reflects accurately quantitative changes of the mucosal mass in the remaining ileum but not in the duodenum, and (2) circulating levels of DAO could be used as a marker of ileal mucosal adaptation after proximal enterectomy.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Morphological and biochemical changes in gastric mucosa of aging rats

Although previous data from this laboratory have indicated that aging is associated with increased gastric mucosal proliferative activity, no direct assessment of proliferative potential of the tissue has been made during aging. In order to assess this, and to determine whether changes in mucosal proliferative potential would be reflected in growth of the tissue, we have examined the labeling index (LI), height and morphology of the gastric mucosa in young (4-month-old) and aged (24-month-old) Fischer-344 rats. In addition, tyrosine kinase (Tyr-k) activity and the levels of phosphotyrosine proteins were determined to evaluate their relationship to mucosal proliferative activity. Histologic evaluation revealed a marked atrophy of the mucosal glandular component with 32% reduction in height in aged rats when compared with young animals. In aged rats, there was also a decrease in gland density, resulting in a reduction in the number of epithelial cells of all types with evidence of decreased secretory activity. Despite the occurrence of mucosal atrophy in aged rats, LI in these animals was significantly increased by 28%. This was associated with a parallel rise in mucosal Tyr-k activity, and a two-to threefold increase in the relative concentrations of seven phosphotyrosine membrane proteins with M_r of 120, 105, 90, 60, 55, 48 and 32 kDa. We conclude that (1) although aging is associated with increased gastric mucosal proliferative activity, this does not result in mucosal growth and that (2) Tyr-k and tyrosine phosphorylation of certain proteins play a role in the regulation of gastric mucosal cell proliferation during aging.     

氨水对大白鼠胃粘膜长期作用的影响：胃粘膜屏障功能的变化

本实验使用0.01％及0.02％的氨水,以自由饮水的形式经口长期喂养大白鼠,观察了氨水对胃粘膜血流、胃粘膜电位差及胃粘膜前列腺素E_2的影响。结果表明:由HP分泌的悄素酶所分解产生的氨长期作用于胃粘膜,可以导致大白鼠的胃粘膜血流和前列腺E_2减少,使胃粘膜电信差降低,破坏胃粘膜的防御机能,可能是HP导致慢性胃炎及胃溃疡的一个重要因素。     

Mucosal Tag of the Duodenum: —Report of a Case—

Abstract: We studied a 66-year-old female who had a dull epigastric pain. An upper gastrointestinal (GI) series revealed a cordlike protrusion in the duodenal region, and a gastroendoscopic examination was performed and revealed a mucosal tag (MT) about 3 cm in length in the duodenal bulb. The MT was resected endoscopically and was found to be lined by normal duodenal mucosa and to have developed hyperplasia of the Brunner's glands. This MT was considered to be a congenitally-developed, hamartomatous hyperplasia of the duodenal mucosa, and of the Brunner's glands in particular.