针灸对胃黏膜保护作用研究述评

胃溃疡(gastric ulcer,GU)的主要发病年龄为45～55岁,男性略多于女性,男女发病约为3:1～10:1[1].

大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

小儿胃黏膜肠上皮化生病理组织学特点

一、材料和方法1.材料:对1990-2004年我科及浙江大学附属儿童医院病理科共12 746例胃镜活检胃黏膜组织进行回顾性研究,其中诊断胃炎伴胃黏膜肠上皮化生55例,男性23例,女性32例,年龄小者3岁,大16岁,平均年龄(9.1±2.8)岁.随机抽取200例经病理诊断胃炎不伴肠化患儿作为对照组.

大鼠应激性溃疡胃黏膜nNOS/iNOS表达对细胞凋亡的影响

目的:探讨细胞间信息传递因子NO在胃黏膜遭受应激损伤时的变化及与细胞凋亡发生的关系.方法:原位末端标记(TUNEL)法检测大鼠水浸-束缚应激(WRS)结束前后不同时间点细胞凋亡的发生;免疫组化的方法检测胃黏膜组织nNOS/iNOS蛋白表达的变化;检测不同剂量的NO合成抑制剂L-NAME对细胞凋亡的影响.结果:iNOS蛋白表达与细胞凋亡的变化呈显著正相关;nNOS蛋白表达与细胞凋亡变化呈负相关;与对照组比较,小剂量L-NAME(2.0 mg/kg)可降低凋亡细胞发生率34.6%(P＜0.01);大剂量L-NAME(20.0 mg/kg)明显增加凋亡细胞发生率25.8%(P＜0.05).结论:正常生理状态下及应激初期,胃黏膜以nNOS表达为主.若应激源持续存在,nNOS表达受抑制,iNOS表达增强,诱导合成大量NO,有明显细胞毒作用,促进细胞凋亡发生.

热休克蛋白在胃黏膜保护中的作用

热休克蛋白在细胞的正常发育和多种应激状态下维持细胞的稳定性具有重要的作用.热休克蛋白有多个家族,他们的细胞内定位和功能各不相同.胃黏膜细胞常常受到食物、酒精、氧化物及幽门螺杆菌感染的刺激,胃黏膜细胞在这些应激状态下会加速热休克蛋白的合成.热休克蛋白表达在转录和翻译两个水平上进行调节.蛋白质缺乏、肾上腺素能神经功能减退将减弱其表达,而迷走神经功能的削弱会增强热休克蛋白的表达;除此之外多种外源性因素也会影响其表达.热休克蛋白对于应激性溃疡的预防、胃黏膜细胞凋亡的抑制均有一定的保护作用.本文综述了主要的热休克蛋白分子的特性、胃黏膜细胞中热休克蛋白的表达诱导、调节以及在胃黏膜保护中的作用,并探讨了热休克蛋白诱导剂作为胃黏膜保护剂的可能性.

胃黏膜癌变过程中PTEN基因编码产物的表达及意义

目的:观察抑癌基因PTEN编码产物在胃黏膜癌变过程中的表达,探讨PTEN表达与胃癌发生的关系.方法:选取胃镜下正常胃黏膜、慢性浅表性胃炎、萎缩性胃炎无肠化、萎缩性胃炎伴肠化、中度不典型增生、重度不典型增生标本各60例,选取手术后早期胃癌、进展期胃癌标本各60例,应用S-P免疫组化方法检测各种胃黏膜病变中PTEN编码产物表达,比较其表达与胃癌发生的关系.结果:PTEN编码产物在正常胃黏膜、慢性浅表性胃炎、无肠化萎缩性胃炎、伴肠化萎缩性胃炎、中度异型增生、重度异型增生、早期胃癌和进展期胃癌中的阳性表达率分别为100%,98.3%,91.6%,78.3%,75%,63.3%,61.7%,43.3%.在检测的120例胃癌中,肠型胃癌76例,PTEN表达率为60.5%,弥漫型胃癌44例,PTEN表达率为38.6%.结论:PTEN基因编码蛋白在胃癌发生过程中进行性下调,PTEN蛋白表达可作为判定胃癌生物学行为的客观指标.

幽门螺杆菌细胞毒素促进胃黏膜分泌白介素8作用

目的:探讨细胞因子在幽门螺杆菌(H. Pylonri)免疫病理机制中的作用.方法:48例患者(慢性浅表性胃炎37例,十二指肠溃疡(DU)11例,其中男性31例,年龄21-63岁)胃镜诊断明确后取胃窦及胃体活检,用于H. Pylori诊断及体外组织培养.H. Pylori诊断采用快速尿素酶试验、H. Pylori培养及Warthin-Starry银染色,3项检查中任2项结果阳性诊断为H. Pylori阳性.3块胃窦活检组织各加1mL RPMI1640,50mL -1CO2和37℃培养24h,ELISA法测上清中白介素(IL)-6,IL-8及肿瘤坏死因子(TNF)-α;Lowry改良法测活检组织蛋白含量.另8例RPMI 1640中加入H.pylori细胞空泡毒素(VacA).结果以每克蛋白中ng(ng g-1)或mg(μg g-1)表示.结果:H. Pylori阳性率69%.H.pylori阳性者胃黏膜培养上清中IL-6,IL-8和TNF-α含量均显著高于H. Pylori阴性者,其中9例DU患者的IL-8含量为53(18-96)μg g-1,显著高于慢性胃炎者的36(7-84)μg g-1(P＜0.01).培养液加入VacA后,IL-8的分泌量明显增高(50±38μg g-1vs 68±30μg g-1,P＜0.01).TNF-α的含量虽升高,但无显著差别,对IL--6的含量无影响.IL-8的含量与炎症程度及活动性显著相关(r=0.98,P＜0.0025),IL-6和TNF-α的含量与炎症程度无明显关系(r=-0.26和-0.28,P＞0.25),但活动性炎时高于非活动性炎者.结论:结果提示IL-8与炎细胞浸润密切相关,H. Pylori细胞毒素对黏膜细胞因子的分泌有促进作用.

AIM To investigate the effects of collagen solution on the prevention of acute gastric mucosal injury inrestricted rats inflicted by cooling in low temperature (4℃),METHODS Thirty healthy Wistar rats were randomly divided into normal (N, n = 10),injury (I, n = 10)and prevention (P, n = 10) groups. The rats were fasted for 48 h but free access to water without restrictionand cooling in normal group, fasted for 48 h but free access to water with restriction of rats onto the fixationframe for cooling in 4℃ for 4 h, so to cause stress injury of gastric mucosal membrane in I group and fed with3 mL of collagen solution 30min before injury in P group in addition to the procedures in I grobp. Gastricmucosal potential difference, blood flow volume, content of nitrite (NO2-) and hydrogen ion concentration(H+ ) in gastric juice were determined under aneasthesia at 48 h after fast in N group and at 4 h after injuryin I and P groups to evaluate the degree of injury (injury index).RESULTS Gastric mucosal potential difference was 22.10±5.27 in N group and 11.46±5.25 in I groupwith obvious difference (P<0.01), but 16.98±4.84 in P group which was remarkably improved whencompared to that in I group. Gastric mucosal blood flow volume was 23.65±10.65 in I group and 57.20±11.75 in N group with evident difference (P<0.01), but 37.49±5.87 in P group with sound effects incontrast to that in I group (P<0.01). Gastric injury index was 18.40±8.35 in I group and 7.9±2.13 in Pgroup with significant difference (P<0.01). Hydrogenion concentration in gastric juice was 118.0±41.2mmol/L in N group, 186.9±74.7 mmol/L in I group and 96.4±57.2 mmol/L in P group with prominentdifference (P< 0.01 ) between those in I and P group. Gastric mucosal nitrite concentration was 1.15±0.46in N group, 0.69±0.15 in I group and 1.04±0.44 in P group with obvious differences between N and Igroups (P<0.01) and between I and P group (P<0.01).CONCLUSION Ischemic and hypoxic injury of gastric mucosal due to low blood perfusion during restrictionand cooling injury at 4℃ was supposed to be an important factor in inducing gastric mucosal stress injury. Butcollagen solution could maintain the integrity of gastric mucosal barrier, buffer gastric acid, promotethrombocytic agglutination and ameliorate direct injury to gastric mucosa caused by various factors.

AIM To investigate DNA methylation status in gastric cancer and its relationship with folate metabolism.METHODS Serum before operation, the gastric mucosa from the lesion, and the surrounding area inpatients with gastric cancer and the remote normal-appearing mucosa of the resected stomach were collectedrespectively. The serum folate, mucosal tissue folate, S-adenosylmethionine ( SAM ), S-adenosylhomocysteine (SAH), and the DNA methylation levels were determined.RESULTS The tissue folate was significantly lower than that in ulcers, especially in the surrounding andnormal mucosa (0.38±0.13, 0.50±0.17 vs 0.53±0.50, 0.79±0.82ng/mg protein, P < 0.01), and itdecreased gradually in the lesion areas. The DNA methylation status showed similar decreasing trend incancers compared with the methylation increasing trend in ulcers. The SAM level ascended in the lesion areaswith a higher. concentration in cancer mueosa (63.5±43.0 vs 25.9±11.9nmol/g tissue, P < 0.01 ). Theaccumulation of SAH in the surrounding and normal mucosa of cancers was observed (17.3±24.6, 15.5±8.6vs 14.6±4.2, 10.0±1.9nmol/g tissue, P < 0.05 - 0.01). There were significantly negative correlationsbetween tissue folate and the SAM and SAH levels in the three areas.CONCLUSION Patients with gastric cancer have the regional folate deficiency in the stomach mucosa,although the serum folate level remains normal. This disturbs the local SAM and SAH metabolism withaccumulation of SAH and DNA hypomethylation which has been known as an important molecularmechanism for carcinogenesis. Folic acid can modulate DNA methylation status by its effect in one-carbongroup metabolism and thus affect the process of the carcinogenesis. Therefore, this may be an access for theprevention of gastric cancer.

AIM To investigate the diagnostic value of CagA IgG in serum.METHODS Seventy three patients with peptic ulcer infected with HP were eradicated by antibioticstherapy. At pretreatment, wk9 and wk20 after treatment, the detection of Hp in gastric muscosa bybacteriologic method were performed, and CagA and whole-cell antigen of HP igG in serum by ELISAmethod were also performed at the same time.RESULTS The IgG titres of Hp CagA and whole-cell antigen changes in accordance with the efficacy ofHp eradicated. The former with an earlier appearance and a greater number of cases decreased to normallevel in comparison with the latter.CONCLUSION CagA IgG is a better index for observing the effectiveness of the eradication of Hp.

AIM To determine the role of Helicobacter pylori in altering gastric mucin synthesis and define how thprocess relates to H. pylori-related diseases.METHODS Analyses of human gastric tissues using immunohistochemistry and in situ hybridizatiodocument the role of H. pylori in altering the composition and distribution of gastric mucins.RESULTS These data indicate a decrease in the product of the MUC5 (MUC5AC) gene and aberraexpression of MUC6 in the surface epithelium of H. pylori-infected patients. A normal pattern was restorby H. pylori eradication. Inhibition of mucin synthesis including MUC5AC and MUCl mucins by H. pvlohas been established in vitro using biochemical and Western blot analyses. This effect is not due to inhibitiof glycosylation, but results from inhibition of synthesis of mucin core structures. In vitro experiments usiinhibitors of mucin synthesis indicate that cell surface mucins decrease adhesion of H. pylori to gastepithelial cells.CONCLUSION Inhibition of mucin synthesis by H. pylori in vivo can disrupt the protective mucous layand facilitate bacterial adhesion, which may lead to increased inflammation in thc gastric epithelium.

AIM To study the combined expression of gastrointestinal hormone substance P and anti-apoptosis gene Bcl-2 in gastric carcinoma and its significance.METHODS Substance P and Bcl-2 protein expression was examined by the S-P immunohistochemicalmethod in 33 cases of gastric carcinoma, 17 adjacent the carcinoma and 13 normal gastric mucoma.RESULTS Positive expression of SP in gastric carcinoma was higher than that of both adjacent and normalmucosa (P < 0.001). There was no statistical difference in the positive expression between adjacent andnormal mucosa (P > 0.05). The expression of bcl-2 both in gastric carcinoma and adjacent tissues werehigher than that of normal gastric mucosa (P< 0.05-0.01). But the positive expression of Bcl-2 had nostatistical significance between gastric carcinoma and adjacent tissues.CONCLUSION Both gastrointestinal hormone SP and Bcl-2 gene have synergistic expression in gastriccarcinoma, indicating that they all take part in the occurrence of gastric carcinoma. Abnormal expression ofBcl-2 gene occurred in benign gastric pathological changes, once they become carcinoma, the positiveexpression of cell is no more increased, possibly because that there is no more increase of the intensity of Bcl-2 inhibition of cell apoptosis.

AIM To study the protective effects of Weitongling decoction (WTL) on gastric mucosa.METHODS Rats with gastric lesion induced by dehydrated alcohol were used to observe the gastric mucosalblood flow (GMBF), rats with spleen deficiency syndrome induced by reserpine were applied to investigatethe D-xylose absorption rate, the Alcian blue binding properties of gastric wall, the gastric acid secretion andthe activity of pepsin.RESULTS Remarkable increases in GMBF (19.5±3.5 mL/min, 20.4±3.3 mL/min respectively in largedose group and small dose group, P<0.01), in Alcian blue binding properties of gastric wall (2.497 mg±0.138 mg, 2.223 ug±0.186 mg respectively in large dose group and small dose group, P<0.05) and in D-xylose absorption rate (1.287±0.043, 1.294±0.019 respectively in large dose group and small dose group,P<0.05) were found after administrations of WTL, while no significant alteration in gastric secretion wasshown and in vitro WTL did not neutralize gastric acid.CONCLUSION WTL can improve the Spleen deficiency syndrome, strengthen the gastric mucosal barrier,and thus protect gastric mucosa against injury agents.

AIM To understand the rule and possible function of apoptosis and protein expression of bcl-2, p53 and C-myc in chronic gastritis, gastric ulcer, non-classic proliferation of gastric mucosa and gastric cancer.METHODS Apoptosis was detected by using in situ terminal labelling (TUNEL). The protein expression ofbcl-2, p53 and C-myc was detected by immunohistochemical method.RESULTS The indexes of apoptosis in chronic active gastritis, gastric ulcer, mild and severe non-classicproliferation of gastric mucosa, early and progressive gastric cancer were 16.8%±12.3%, 24.1%±20.0%,19.3%±16.4%, 15.7%±15.2%, 10.1%±9.1% and 6.3%±6.0%, respectively. The index of progressivegastric cancer was lower than that of early gastric cancer and non-classic proliferation of gastric mucosa(P<0.05). The positive rate of bcl-2 protein was 9.4%, 27.6%, 52.9%, 75.0%, 83.3% and 46.7%,respectively. The positive rate of bcl-2 of early gastric cancer was higher than that of progressive gastriccancer. The positive rates of p53 protein of severe non-classic proliferation, early and progressive gastriccancer were 25.0%, 33.3% and 63.3%, respectively. The positive rate of p53 of progressive gastric cancerwas higher than that of early gastric cancer and non-classic proliferation (P<0.05). In Lauren types, theindex of apoptosis, protein expression rates of bcl-2, p53 and C-myc of intestinal type were 8.3%±7.2%,38.9%, 77.7% and 56.6%, while that of diffuse type were 5.1%±4.9%, 58.3%, 50.0% and 8.3%,respectively. All markers had statistical difference between two types (P<0.05).CONCLUSION Apoptosis was inhibited stepwise in the development of non-classic proliferation of gastricmucosa to early gastric cancer and then to progressive gastric cancer. The high expression of bcl-2, p53 andC-myc was related to the development of gastric cancer, bcl-2 might play an important role in early gastriccancer while p53 and C-myc act mostly in middle and late stage gastric cancer. The Lauren typing of gastriccancer is closely related to the index of apoptosis and expression of bcl-2, p53 and C-myc.

AIM To observe the predictive value of gastric intramucosal pH (pHi) for critical patients.METHODS The gastric intramucosal pH (pHi) of 32 ICU patients was measured with a self-madegastrointestinal tonometer, and the APACHE l score was determined simultaneously.RESULTS pHi of the nonsurvivors was significantly lower than that of the survivors (P<0.05). The pHiwas remarkably higher in the nonsepsis group than in the sepsis group (P<0.01). Only in multiple organfailure groups, pHi was found statistically lower (P<0.05).CONCLUSION pHi may be the most simple, reliable, sensitive and accurate parameter to indicate theadequacy of tissue oxygenation, and it may be widely used in ICU monitoring in near future.

AIM To study the agglutination pattern of Helicobacter pylori coccoid and spiral forms.METHODS Assays of agglutination and agglutination inhibition were applied using fifteen commercial lectins. RESULTS Strong agglutination was observed with mannose-specific Concanavalin A (Con A ),fucose-specific Tetragonolobus purpureas ( Lotus A ) and N-acetyl glucosamine-specific Triticum vulgaris (WGA) lectins. Mannose and fucose specific lectins were reactive with all strains of H. pylori coccoids as compared to the spirals. Specific carbohydrates, glycoproteins and mucin were shown to inhibit H. pylori lectin-agglutination reactions. Pre-treatment of the bacterial cells with formalin and sulphuric acid did not alter the agglutination patterns with lectins. However, sodium periodate treatment of bacterial cells were shown to inhibit agglutination reaction with Con A, Lotus A and WGA lectins. On the contrary, enzymatic treatment of coccoids and spirals did not show marked inhibition of H. pylori-lectin agglutination. Interestingly, heating of H.pylori cells at 60℃ for 1 hour was shown to augment the agglutination with all of the lectins tested. CONCLUSION The considerable differences in lectin agglutination patterns seen among the two differentiated forms of H. pylori might be attributable to the structural changes during theevents of morphological transformation,resulting in exposing or masking some of the sugar residues on the cell surface. Possibility of various sugar residues on the cell wall of the coccoids may allow them to bind to different carbohydrate receptors on gastric mucus and epithelial cells. The coccoids with adherence characteristics like the spirals could aid in the pathogenic process of Helicobacter infection.This may probably lead to different clinical outcome of H. pylori associated gastroduodenal disease.

早期肠内营养对重度脑外伤胃黏膜的影响及护理

重度脑外伤病人易并发应激性溃疡、肠源性感染,这与其创伤后胃黏膜低灌注致胃肠黏膜屏障损害密切相关.20世纪80年代以来,一种简便、微创的监测指标胃黏膜pH值、Pg-aCO2(胃黏膜表面CO2张力和动脉血CO2之差)用于临床,可敏感的反映胃肠道局部血流和组织氧合状况,较现有的一些循环监测指标,如剩余碱、氯、动脉血乳酸盐浓度等更为及时和可靠[1].本文通过对胃黏膜pH、Pg-aCO2的监测,探讨早期肠内营养对重度颅脑损伤后胃肠黏膜屏障是否具有保护作用.

电针足三里对应激大鼠血浆表皮生长因子和降钙素基因相关肽的影响

Objective To study the effect of electroacupuncture (EA) on epidermal growth factor( EGF),calcitonin gene-related peptide(CGRP) and gastric mucosa in stress rats. Methods 72 SD rats were randomized into 3 groups:control group,stress group and EA group.Each group were divided into 3 small groups by 1,3,5 d test time.By radioactive-immunon-assay and Guth methods, ;the changes of EGF.CGRP in plasma and ulcer index (UI) were analyzed. Results Stress group compared with control group, the level of EGF decreased (P< 0.05);but UI increased (P< 0.01).In the EA group compared with stress group, plasma EGF increased (P< 0.05);but UI decreased (P< 0.01).The changes of CGRP in test 5d was more obvious than in 1d in EA group (P< 0.01).Conclusion EA can protect gastric mucosa in stress rats, EGF, CGRP take part in this function.CGRP in EA group can be effected by test time.

上食管异位胃黏膜19例分析

上食管异位胃黏膜(heterotopic gastric mucosa in the up-per esophagus,HGMUE)是指胃黏膜出现于食管上段,且可引起临床症状的一种疾病,临床少见.本文总结浙江大学医学院附属第二医院和浙江省肿瘤医院2000～2002年6000余例内镜检查中发现的19例患者的临床、内镜下特点.

上食管异位胃黏膜氩离子凝固术治疗39例

上食管异位胃黏膜(heterotopic gastric mucosa in the up-per esophagus,HGMUE)是指胃黏膜出现于食管上段,且引起临床症状的一种疾病.因其位于颈段食管,在胃镜检查时常被漏诊或误诊.自2006年1月到2007年12月,我们在10000余例胃镜检查中发现39例该病患者,行病理学检查确诊后进行了内镜下氩离子凝固术(APC)治疗,报道如下.