幽门螺杆菌感染Balb/c 小鼠模型的建立及对N-甲基-N-亚硝基脲诱发胃癌的影响

目的建立一种稳定的造模周期短的幽门螺杆菌(Hp)感染模型,观察Hp对小鼠胃黏膜的损害程度,同时研究Hp感染是否促进亚硝基类化合物的致癌作用.方法 94只Balb/c小鼠分为4组.第1组单用N-甲基-N-亚硝基脲(MNU);第2、3组小鼠用灌胃法定植Hp,第3组小鼠加用MNU灌胃;第4组为正常对照.36周后处死全部小鼠,分别用尿素酶、Giemsa染色和微需氧细菌培养检测Hp定植;H-E染色进行鼠胃黏膜病理诊断.结果 Balb/c小鼠Hp定植率达93.9%.Hp单一处理组中度以上炎症占100.0%,其中萎缩性胃炎占20.0%;而Hp和MNU联合处理组中度以上炎症占100.0%,其中萎缩性胃炎占23.1%,不典型增生占42.3%和57.7%(胃体和胃窦),并发现2只小鼠有低分化腺癌,占7.1%.Hp处理组和Hp MNU联合处理组在炎症程度上与正常对照组相比,差异有统计学意义(P＜0.01).结论本实验成功建立了Hp感染小鼠模型,验证了Hp和胃癌的发生有高度相关性,证实Hp在协同MNU致癌性中的作用,提示胃癌的发生并非Hp感染单一因素的结果,而和多因素共同作用有关.     

大肠腺瘤的治疗

随着人们生活水平的提高和医疗条件的改善,诸多急性传染病均得到了有效的控制.然而,一些与环境因素密切相关的慢性非传染性疾病,如心、脑血管疾病和恶性肿瘤的发病率有了明显上升.大肠癌便是一个突出的例子.欧美和日本等大肠癌高发国家的研究证明,长年的高蛋白、高脂肪和低纤维素饮食习惯是促发大肠癌的重要环境因素(外因),患者遗传上的缺陷,如多种病相关基因的突变又是大肠癌发病的内在因素,这些相关的内外因素结合在一起可能也是近年我国大肠癌发病率上升的重要原因之一.预防为主是我国一贯的卫生工作方针,也是大肠癌防治工作的重点,纠正不良的饮食习惯,深入研究大肠癌发病的分子机制,从病因上着手防病是大肠癌预防工作的一级预防,而提高早癌和癌前疾病的检出率则是大肠癌的二级预防.众所周知,大肠癌有两个特点:一是有明确的癌前病变(93％的大肠癌来源于腺瘤);二是从癌前病变发展为癌有一较长的过程(平均7a).我们可以利用这些特点,通过普查发现癌前病变和早期癌,经过内镜的微创治疗,预防大肠癌的发生,提高早癌治愈率.下面几篇论文将围绕大肠癌早诊、早治的问题进行初步讨论,希望能引起同行专家的兴趣,提出更深入的见解.     

牛磺酸对四氯化碳诱导大鼠肝纤维化的抑制作用

目的研究牛磺酸的体内抗肝纤维化作用。方法用四氯化碳（ＣＣｌ４）复制大鼠肝纤维化模型;造模开始或造模６周后给予牛磺酸;实验结束后分别测定肝功能、纤维化指标（透明质酸和层粘连素）、肝羟脯氨酸及Ⅰ、Ⅲ型前胶原ｍＲＮＡ含量,并作肝病理检查。结果牛磺酸可显著减轻ＣＣｌ４肝纤维化程度,能明显降低肝羟脯氨酸和Ⅰ、Ⅲ型前胶原ｍＲＮＡ含量,降低血清透明质酸和层粘连素水平,改善肝功能,组织学检查亦显示具有抗肝纤维化作用。结论牛磺酸在体内具有抗肝纤维化的作用,可望用于肝纤维化的防治。     

双歧杆菌对实验性大肠癌的抑制作用及其机制的初步探讨

双歧杆菌对实验性大肠癌的抑制作用及其机制的初步探讨王立生潘令嘉施理张亚历周殿元Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｂｉｆｉｄｏｂａｃｔｅｒｉｕｍｌｏｎｇｕｍ；ｃｏｌｏｎｉｃｎｅｏｐｌａｓｍｓ；ｎｅｏｐｌａｓｍｔｒａｎｓｐｌａｎｔａｔｉｏｎ；ｄｉｓｅａｓｅ...     

5-氨基水杨酸联合尼美舒利对结肠癌细胞株HT-29增殖的影响

研究表明5-氨基水杨酸（5-ASA）和非甾体抗炎药（NSAIDs）对结直肠癌具有化学预防作用，但目前关于两类药物联合应用对结直肠癌影响的文献较少。目的：研究5-ASA联合选择性环氧合酶-2抑制剂尼美舒利对人结肠癌细胞株HT-29的增殖抑制作用及其可能机制。方法：采用甲基噻唑基四唑（MTr）比色法测定5-ASA、尼美舒利单独以及联合应用抑制HT-29细胞增殖的作用，分别采用原位末端标记（TUNEL）和免疫细胞化学方法检测细胞凋亡和增殖细胞核抗原（PCNA）的表达。结果：1—1000μmol／L5-ASA或尼美舒利单独应用对体外培养的HT-29细胞具有明显增殖抑制作用，呈剂量依赖性；两者在100μmol／L剂量下分别作用12—96h，抑制率逐渐增高，呈时间依赖性。20～2000μmol／L 5-ASA与尼美舒利联合应用能明显抑制HT-29细胞增殖，呈剂量和时间依赖性，且优于单独应用5-ASA或尼美舒利（P〈0．05）。10—500μmol／L 5-ASA和尼美舒利单独或联合作用于HT-29细胞，细胞凋亡率逐渐增高，PCNA表达逐渐降低，与单独应用相比，联合用药作用更强（P〈0、05）。结论：5-ASA联合尼美舒利具有抗HT-29细胞增殖的作用，其作用优于单独应用5-ASA或尼美舒利。     

实验性胃癌模型的研究

实验性胃癌模型的研究梁卫江１，２黄卓垣１丁彦青１Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｓｔｏｍａｃｈｎｅｏｐｌａｓｍｓ／ｐａｔｈｏｌｏｇｙ；ａｄｅｎｏｃａｒｃｉｎｏｍａ；ｄｉｓｅａｓｅｍｏｄｅｌｓ，ａｎｉｍａｌ主题词胃肿瘤／病理学；腺癌；疾病模型，动物中...     

N-甲基-N′-硝基-N-亚硝基胍胃癌前病变大鼠造模联合因素的探讨

N-甲基-N′-硝基-N-亚硝基胍（MNNG）是目前使用最广泛的胃癌癌前病变（PLGC）大鼠模型的造模用药,但造模时间过长。多种因素联合造模可缩短造模时间,促进造模效果。国内外文献中,除MNNG外,还有其他多种理化造模因素可供选用,是否适合与MNNG联合造模,笔者探讨如下。     

鱼腥草治疗溃疡性结肠炎大鼠对结肠压力的影响

溃疡性结肠炎患者（ＵＣ）经常有腹痛,腹泻等临床表现,这些症状与结肠动力紊乱密切相关［１,２］,但目前尚缺少一种理想的检测结肠动力的方法,如常用的大鼠离体结肠压力测定,不仅需要麻醉,手术,开腹,而且离体肠段保存条件很难与在体状态一致,影响了检测结果的准...     

异常隐窝病灶与大肠肿瘤关系及发生途径的初步研究

目的 实体镜下连续观察Wistar鼠大肠癌模型中异常隐窝病灶(ACF)的发生情况,探讨ACF与大肠肿瘤的相关性及其发生途径.方法 60只Wismr鼠给予二甲肼皮下注射,每周1次,连续18周,分组处死.将美蓝染色后的大肠组织在实体镜下观察.结果 发现2种不同镜下表现的ACF,即cACF和dACF.dACF与大肠肿瘤形成早期有相似的镜下形态及病理特点,而cACF则无类似特征.cACF与dACF在β-catenin中的表达异常率分别为4.8%和100.0%(P=0.000),在MMP-7中的阳性表达率分别为7.9%和81.8%(P=0.000),dACF与肿瘤在β-catenin的表达异常率以及在MMP-7的阳性表达率上的差异均无统计学意义(P>0.05).结论 cACF与肿瘤发生无明显相关,dACF与肿瘤发生关系密切,其发生遵循Wnt途径.     

Inhibitory effect of sulindac against chemically-induced primary colonic tumors by N-methyl-N-nitrosourea in mice

AIM: To investigate the chemopreventive effect of sulindac, a nonsteroidal anti-inflammatory drug (NSAID), on the growth of N-methyl-N-nitrosourea (MNU)-induced mouse colonic tumors.METHODS: The experimental colonic tumor model induced by intrarectal instillation of MNU in mice was used in the present study. In the first experiment, MNU intrarectal was instilled and sulindac administered concurrently to a group of mice for a period of 18 wk, while a control group of animals received MNU only for the same period. In the second experiment, two groups of mice that had already been treated with MNU for 12 wk received sulindac or not for another 18 wk.RESULTS: The tumors induced in mice were all located in the distal part of the large intestine. There were no significant differences in the location and the gross appearance of the tumors in the MNU-induced group and control group in both experiments. In the first experiment, sulindac caused a significant reduction in both the number of mice with colonic tumors and the number of tumors per mouse. Sulindac had a significant inhibitory effect on the growth of the MNU-induced tumors. However, in the second experiment, the inhibitory effect of sulindac was less or disappeared.CONCLUSION: Sulindac has a protective effect against the chemical induction of colonic tumors by MNU in mice. The chemopreventive effect is more significant in the initial stage of the tumor, while in the promotion stage this effect is less or disappeared. Sulindac can not cause the regression of established tumors.     

丁酸盐与非甾体抗炎药对大肠腺癌细胞HT-29的作用

目的 观察丁酸盐和非甾体抗炎药（NSAIDs)对大肠腺癌细胞HT－29的作用,并探讨其可能的作用机制。方法 用酶联免疫法定量检测HT－29细胞所分泌的前列腺素（PG）E2;流式细胞仪检测细胞的凋亡率;电镜观察凋亡细胞的形态学。结果 丁酸盐可刺激细胞分泌大量的PGE2,阿司匹林和NS－398则抑制PGE2的分泌,3种药物均具有促进细胞凋亡的作用,且其作用呈浓度和时间依赖性（P＜0．05）;药物联用可使其作用不同程度地增强。结论 单用丁酸盐和2种NSAIDs制剂均有促凋亡作用,联用可通过下调环氧化酶－2的表达进一步增强疗效。     

Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice

Background and Aims: The pathogenesis of enteropathy induced by non‐steroidal anti‐inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin‐17A (IL‐17A) is a pro‐inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL‐17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL‐17A gene. Methods: Male C57BL/6 (wild‐type) and homozygous IL‐17A^‐/‐ C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small‐intestinal damage. Indomethacin‐induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. Results: The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory‐associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein‐1 (MCP‐1), and granulocyte‐colony stimulating factor (G‐CSF), were significantly increased in indomethacin‐treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL‐17A^‐/‐ mice compared with wild‐type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP‐1, and G‐CSF levels. Conclusion: These findings demonstrate that IL‐17A contributes to the development of indomethacin‐induced small intestinal injury through upregulation of G‐CSF, KC, and MCP‐1. IL‐17A might be a promising new therapeutic target to treat NSAID‐induced enteritis.     

牛磺酸对三硝基苯磺酸诱导的结肠炎大鼠肠纤维化的抑制作用

目的 探讨牛磺酸对三硝基苯磺酸(TNBS)诱导的结肠炎大鼠肠纤维化的影响.方法 32只SD大鼠均分为对照组、模型组、低剂量和高剂量牛磺酸组.对照组以0.9%氯化钠溶液灌肠,其余3组以TNBS灌肠诱导建立结肠炎模型.低剂量和高剂量牛磺酸组于造模前1周每日分别给予牛磺酸400和800 mg/kg干预,直至造模结束.观察大鼠临床表现及疾病活动指数(DAI),行结肠大体评分和组织学评分,检测大鼠结肠长度、结肠重量.测定结肠组织中羟脯氨酸(Hyp)、Ⅰ型胶原蛋白、转化生长因子-β1(TGF-β1)蛋白和mRNA、Smad3蛋白和mRNA水平.结果 与对照组相比,模型组大鼠体重减轻、DAI评分升高、结肠狭窄伴近端扩张、结肠长度缩短、结肠重量增加、大体评分也显著升高(P<0.01).牛磺酸干预后,大鼠体重、DAI评分、结肠长度等指标均有所改善.模型组纤维化评分为1.88±0.35.较对照组明显增加(0.25±0.46,P<0.01);低剂量和高剂量牛磺酸组纤维化评分分别为1.25±0.71和0.75±0.47,较模型组下降(P<0.05).模型组大鼠结肠Hyp、TGF-β1、Ⅰ型胶原蛋白、Smad3蛋白和mRNA含量均较低剂量和高剂量牛磺酸组明显上升(P值均<0.05).结论 牛磺酸能有效抑制TNBS诱导的结肠炎大鼠肠纤维化,其抗纤维化机制可能与下调TGF-β1、抑制TGF-β/Smad3通路有关,为解决克罗恩病肠纤维化和肠狭窄提供一定的实验依据.     

姜黄素对胆汁酸诱导的人结肠癌细胞HT-29增殖的抑制作用

/L、作用6 h时和浓度≥0.5μmol/L、作用12 h时,即可抑制DCA诱导的COX-2 mRNA表达;姜黄素浓度≥1μmol/L、作用24～48 h和浓度>5 μmol/L、作用6～12 h,即可抑制DCA诱导的COX-2蛋白表达和PGE2合成.结论 姜黄素可以浓度和时间依赖模式抑制DCA诱导的HT-29细胞的增殖、COX-2 mRNA和蛋白的表达以及PGE2的合成,这可能是姜黄素抑制HT-29细胞增殖的机制之一.     

针刺调整实验性家兔胃节律紊乱的研究(英文)

目的建立实验性家兔胃节律紊乱模型，观察腧穴之间针刺调整胃节律紊乱的差异性，以期为临床针刺治疗提供选穴的实验依据．方法家兔６０只，体重２０ｋｇ～２５ｋｇ，禁食１２ｈ～１４ｈ，浆膜下双极胃电引导，用旋转的方法建立家兔节律紊乱模型，观察针刺足三里、内关、条口、天泉穴对胃电紊乱波及胃电频率调整效应的差异．结果足三里与内关穴组针刺前紊乱波百分数分别为５７０７８５±１０２６４４和５５５１７３±６０５００，针刺后分别为４３７８２３±１０１５１８和４３５１４７±６８９８３；针刺前频率分别为２２８７０±０３８００和２４０２０±０３５３６，针刺后分别为２７０９０±０５８６５和２９２２０±０４９２３．均呈现统计学显著性差异（Ｐ＜００５）．但二组穴位之间比较无显著性差异；非特定穴条口、天泉针刺前后对照无统计学显著差异．特定穴足三里与同经非特定穴条口，特定穴内关与同经非特定穴天泉调整效应呈现显著性差异．结论本模型适用于针刺调整胃节律紊乱的研究；特定穴足三里、内关对胃节律紊乱有明显的调整作用．     

Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice

Abstract: Previous research has shown that antioxidant (butylated hydroxyanisole) treatment ameliorates respiratory syncytial virus (RSV)‐induced disease and lung inflammation. Melatonin has been reported to exhibit a wide varieties of biological effects, including antioxidant and anti‐inflammation, and has no evident toxicity and side effect. But it is not known whether melatonin would modify RSV‐induced lung disease and oxidative stress. The present study was to establish the involvement of oxidative stress in the pathogenesis of RSV‐induced lung inflammation, and to investigate the protective effect of administration of melatonin in mice with RSV‐induced oxidative pulmonary injury for 4 days. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated in lung tissue homogenates by spectrophotometry. Hydroxyl radical (˙OH), one of the indicators of free radical formation, was also detected in lung homogenates by Fenton reaction. Tumor necrosis factor‐a (TNF‐a) concentrations in mouse serum were measured with ELISA assay. The results demonstrated that the mice intranasally inoculated with RSV resulted in oxidative stress changes by increasing NO, MDA and ˙OH levels, and decreasing GSH and SOD activities, whereas administration of melatonin significantly reversed all these effects. Furthermore, melatonin inhibited production of proinflammatory cytokines such as TNF‐a in serum of RSV‐infected mice. These results suggest that melatonin ameliorates RSV‐induced lung inflammatory injury in mice via inhibition of oxidative stress and proinflammatory cytokine production and may be as a novel therapeutic agent in virus‐induced pulmonary infection.