【作者】 徐妙；

【导师】 姒健敏；

【作者基本信息】 浙江大学 ， 内科学， 2002， 硕士

【摘要】 慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是一种比较顽固的消化系统常见病、多发病。由于其与胃癌的发病率呈显著相关性，早在80年代，WHO就已将CAG定为胃癌前期状态。据统计约50％左右胃癌在CAG基础上发生，而减少胃癌死亡率最有效的方法是一级预防，因此，如何有效地阻断、干预CAG发生并使其逆转是目前胃癌研究领域的热点。由于该病的病因复杂和发病机制尚不十分清楚，因而缺乏理想的治疗方法。近来研究发现中医药对CAG可能有治疗作用。云母作为中医矿物药之一，首载于《神农本草经》，其性能：甘、平，入肺、肝、膀胱经，有安神、敛疮、止血之功效。古今医家对其作过一些临床观察和研究认为云母有促进细胞的生长，组织愈合及保护胃黏膜的作用。现云母的结构式已明确，但有关云母对CAG(中医属胃痞范畴)转归作用的病理和药理研究尚属空白，许多作用尚待现代医学手段来证实。本研究采用姒氏CAG制模方法：运用60％的酒精，20mmol／l的去氧胆酸钠和0.1％的氨水在24周建立大鼠CAG模型。一方面在制模的同时用云母进行干预；另一方面制模成功后用云母进行治疗，并以硫糖铝作为对照。以研究云母对CAG的干预及治疗作用，为临床寻找出一个有效防治CAG的新药。 材料和方法 选健康、性成熟、一级质量标准的雌性SD大鼠，体重200±10g，共80只，随机分成8组即正常对照组、模型对照组、云母低剂干预组、治疗组、云母高剂干预组、治疗组及硫糖铝干预组、治疗组。模型对照组按本实验室确立的姒氏CAG制模方法制模，干预组在制模的同时分别用云母80mg／100g／d及160mg／100g／d、硫糖铝160mg／100g／d进行干预，每天上午灌胃一次，共24周；治疗组在制模成功后按上述剂量进行治疗，每天上午灌胃一次， 共8周。24周及32周后用颈椎脱臼法处死大鼠后立即剖腹暴露全胃，在距贲门和幽门1．scm 处离断，取出全胃，沿胃大弯切开，观察胃粘膜的色泽、弹性、皱劈情况、粘液多少等大 体情况。然后用生理盐水冲洗后，立即以10％的中性甲醛溶液固定，送病检，分别沿小弯 侧和大弯侧条状取材，石蜡包理切片，分别行HE染色，并在光镜下观察胃粘膜炎症情况， 胃粘膜腺体厚度几1）和粘膜肌层厚度（LZ）之比几1／LZ），单位长度（lin）内胃勤膜腺体数 目。 结果与讨论 干预实验显示： 模型组的大鼠均有不同程度的恶心、流涎、精神萎靡、食欲差、活动减少，体重增长 慢、毛发发黄，光泽度差等。其余各组毛发色白，光泽度好，活动自如。正常组大鼠胃勤 膜呈粉红色，有光泽，被覆较多劾液，剩膜皱劈表面光滑，走向规则，胃壁弹性良好。模 型组胃壁弹力减弱，彩膜层变薄，色苍白，皱劈变平或走向紊乱，可见不同程度的陈旧性 出血点，伴胃窦默膜点状或灶状糜烂。而云母高低剂量干预组肉眼观与正常组无明显差别。 病理切片检查显示：云母高低剂量干预组大鼠胃粘膜上皮细胞排列整齐，腺体排列紧密规 则，胃小凹清晰，除胃窦部可见个别炎细胞外，其余部位极少见到炎细胞及充血、水肿。 胃窦固有层腺体饱满清晰，与胃小凹分界明显，粘膜肌层较薄。胃体部固有腺分布规则， 壁细胞数量丰富，染色均匀，腺体之间排列紧密，无出血、肠化、增生等现象，接近正常 对照组。胃窦部的胃粘膜炎症情况，胃粘膜腺体厚度（LI）和粘膜肌层厚度（LZ）之比（L／L2）， 单位长度内胃劲膜腺体数目与模型对照组有显著的统计学差异（p＜0刀1），而与正常对照组 相比则无明显差别（p＞00引。提示云母有明显的抗化学性损伤因子，保护胃郭膜，从而防 止CAG的发生。各组胃体部均无明显差别，系病变部位以胃窦部多见，而胃体部病变较少。 因而云母亦无保护作用可言。 治疗实验显示： 模型对照组胃窦粘膜腺体有不同程度的排列紊乱、稀疏，粘膜肌层增厚，向粘膜固有 层伸展呈分枝状插入腺体之间，伴有大量炎症细胞浸润，部分有成堆淋巴细胞聚集灶。此 外还发现胃窦粘膜内有腺体囊样扩张，但未发现肠上皮化生、假性幽门腺化生、不典型增 生、腺瘤、类癌、腺癌等。而经云母高低剂量治疗组治疗8周后表现为云母高低剂量组、 胃窦部的胃粘膜炎症情况，胃粘膜腺体厚度（LI）和粘膜肌层厚度（L2）之比（LI／LZ），单位长 度内胃劲膜腺体数目与模型对照组有显著的统计学差异（p＜001）而与正常对照组相比则 2 无明显差别…＞0刀5人各组胃体部均无明显差别，系病变部位以胃窦部多见，而胃体部病 变较少。可见云母对大鼠胃窦勤膜有更多还原

【Abstract】 Chronic Atrophic Gastritis (CAG) is a common disease in clinic. Because of its positive correlation with morbidity of gastric carcinoma, it was considered as a precancerous condition by World Health Organization (WHO). For this reason, to prevent and cure CAG plays a very important role in preventing gastric carcinoma. In this study, we reestablished an animal model of rats with CAG in accordance with the previous experience of combined administration of 60% ethanol, 20mmol/L sodium deoxycholate and 0.1% ammonia water. In one group, sucralfate and isinglass were used as preventive therapy while we were establishing CAG rat model. In the other group, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. To explore a new method of preventing and treating chronic atrophic gastritis is the ultimate aim of this study.Materials and Methods80 healthy, sexual mature, qualified female SD rats were tested, weighting 200+lOg, provided by Zhejiang Medical Institute. All the rats were randomly divided into 8 groups. The rats in Normal Control Group were raised in a routine way for 32 weeks. The rats in Model Control Group were administered with 60% ethanol, 20mmol/L sodium deoxycholate and 0.1% ammonia water for 24 weeks. Then they were fed in a routine way for 8 more weeks. Three groups of rats under prevention test were administered by isinglass 160mg/100g/d, 80mg/100/dand sucralfate 160mg/100g/d respectively in each morning for 24 weeks. Three groups of rats in reverse test were continuously administered by isinglass 160mg/100g/d, 80mg/100g/d and sucralfate 160mg/100g/d respectively in each morning for 8 more weeks after the CAG model was established. Then these rats were anaesthetized by 1% thiopental sodium in foodless condition. 5ml/per blood were taken from carotid through catheter. All rats were executed by dislocation of cervical vertebra and their stomachs were removed and observed the gastric plica,elasticity and luster. The gastric streak-like samples for histological examination were cut along their lesser curvature and greater curvature respectively. Then they were immediately immersed in 10% buffered formalin and embedded in the paraffin. Paraffin sections were cut, mounted on glass slides, and stained with hematoxylin and eosin (HE) to observe a series of indices as follow: (1) Inflammation grade of gastric antrum and body basing on semi-quantity, (2) Ratios of the thickness of gastric mucosal gland and muscularis mucosa(Ll/L2), (3) The number of gastric glands inl-mm lengths of mucosal layer in longitudinal sectionsResults and DiscussionThe experimental results showed the rats in isinglass prevention groups and reverse groups were brisker and heir hairs were whiter and more lustrous than those in CAG model. And the gastric plica, elasticity, luster of rats in the former groups were better than those in letter groups. There were more mucus adhered to the gastric mucosal surface of the rats in the former group than in the latter groups, in which there were obsolete petechia, spot- like or speckle-like erosions in the gastric mucosal surface.The experimental results showed the CAG model was successfully established by administration of 60% ethanol, 20mmol/L sodium deoxycholate and 0.1% ammonia water. HE slides revealed: mucosal glands reduced and arrayed disorderly. Mucosal muscle layer became thick. Plenty of Inflammatory cells immersed in gastric mucosa, partly congregated. No intestinal metaplasia and atypical hyperplasia were found.Pathological patterns of isinglass prevention groups were similar to that of normal control group. However pathological patterns of isinglass reverse group were much better than that of model control group, even close to that of normal control group. HE slides revealed: mucosal glands arrayed closely and regularly. Only a few of inflammatory cells were found.After preventive treatment with isinglass, the inflammation grade, the means of L1/L2, 1-mm lengths of mucosal layer in longitudinal sections of gastric ant更多还原