【作者】 李浩；

【导师】 李哲浩；

【作者基本信息】 延边大学 ， 普通外科学， 2002， 硕士

【摘要】 梗阻性黄疸（Obstructive jaundice）急性胃粘膜病变引起的胃肠道出血，因其死亡率和并发症率高，发病机制不明确，而受到普遍的重视。目前国内外尚无有关梗阻性黄疸应激状态下一氧化氮对胃粘膜损害作用的研究报道，本实验的目的在于，通过观察梗黄及应激大鼠胃分泌、血浆一氧化氮含量的变化及胃组织iNOS的变化，研究梗阻性黄疸急性胃粘膜病变的发病机制，为临床防治提供理论依据。方法：选用健康Wistar雌性大鼠32只，体重250±30g，随机分成2大组，每组16只，即假手术组和梗阻性黄疸组。2周后于实验当天各组再随机分为对照组和应激组，每组8只。收集的胃液分别测定其量、胃蛋白酶活性、总酸度及游离酸度；采集的血液测定一氧化氮、总胆红素及SGPT的含量；切取的胃判定胃粘膜损伤指数后制成蜡块，在HE和ABPAS染色下观察一般形态学及中性粘液的面密度，最后利用原位杂交技术测定胃组织iNOS的含量。结果：⑴梗阻性黄疸组及梗阻性黄疸应激组（以下简称梗黄组及梗黄应激组）与假手术组、假手术应激组（以下简称应激组）相比较，总胆红素及谷丙转氨酶（SGPT）含量明显增加，具有显著性差异（P<0.01）。⑵观察胃粘膜损伤指数，梗黄应激组损伤最严重，其次为应激组、梗黄组，而假手术组未见胃粘膜损伤，各组间均有显著性差异（P<0.01）。⑶应激状态下胃液中的总酸度、游离酸度、胃蛋白酶活性及胃粘膜中性粘液的量增高，具有显著性差异（P<0.05）。⑷梗黄组、梗黄应激组一氧化氮的含量比假手术组、应激组明显增高，且各组之<WP=4>间均有显著性差异(P<0.01)。假手术组iNOS未表达，梗阻性黄疸时iNOS显著高于其它两组(P<0.01)。⑸肉眼观察梗黄及应激时胃粘膜可见点状或条状出血偶见小溃疡灶。显微镜下观察；HE染色：假手术组胃粘膜未受到破坏；其他三组粘膜的完整性遭到破坏，粘膜层部分细胞坏死，细胞核消失，粘膜下出血，血管扩张，血液淤滞，梗阻性黄疸组还可见粘膜层出现胆汁颗粒。Mowry阿尔辛篮过碘酸雪夫（ABPAS）染色：假手术组各层结构均未见异常，粘膜表面被覆上皮完整，其他各组均有病理改变，被覆上皮的完整性遭到破坏，各种粘液细胞增多，腺体扩张等。原位杂交DAB染色：假手术组均未见到iNOS阳性细胞，其他组胃粘膜全层均可见到阳性细胞，包括粘膜层及粘膜下层的细胞、血管壁。结论：⑴梗阻性黄疸大鼠胃粘膜损伤指数增加，应激状态下损伤指数显著增加，提示梗阻性黄疸时胃的损伤因素明显增强。⑵梗阻性黄疸及其应激大鼠血浆NO、胃壁组织iNOS 显著增加，是导致梗阻性黄疸急性胃粘膜病变的病理基础。更多还原

【Abstract】 Acute gastric mucosa pathological changes of obstructive jaundice (OJ)can cause gastrointestinal bleeding and its mortality and complication rate are very high. However, the mechanism is undefined. There is no report about the impairment effect of NO to gastric mucosa in stress state of obstructive jaundice. The purpose of this study is to investigate the mechanism of acute gastric mucosa pathological change of obstructive jaundice and to provide theory for clinical prevention and therapy through observing the change of stomach secretion, the plasma NO content and stomach tissue iNOS. METHODS: In this study, 32 female Wistar rats (weight 250+30g ) were divided into 2 random groups: fake operation(FO) (N=16);obstructive jaundice (OB)(N=16). Two weeks later, each groups were divided into 2 random groups respectively: control(C)(N=8) and stress(S)(N=8).The content of plasma NO; total bilirubin and Serum glutami pyruvate transaminase ( SGPT) and the volume of gastric juice ; pepsin activity; total acidity and free acidity were measured. After gastric mucosa injury index determination, stomach samples were made into paraffin sections, and the HE and ABPAS staining for common morphology and neutral mucus area density ware performed. Hybridization in situ for iNOS of tissue of<WP=6>stomach was performed. RESULTS: (1) Compared with FO and FO+S groups, in OJ and OJ+S groups, increase in total bilirubin and SGPT ware statistically significantly (P<0.01). (2) AS to gastric mucosa injury index, OJ+S group was the most serious; the next was FO+S and OJ groups were less, and there were no gastric mucosa damage in FO group, the differences ware significant (P<0.01 respectively) between each groups. (3) Compared with contrasts, in stress state, increase in pepsin activity; total acidity and free acidity of gastric juice and the content of neutral mucus of gastric mucosa was statistically significantly (P<0.01). (4) The content of plasma NO in OJ and OJ+S groups increased more significantly than FO and FO+S groups, there was differences between each groups (P<0.01, respectively). There was no iNOS expression in FO group and in OJ group and the increase of iNOS expression was stastitically significant (P<0.01) compared with the other 2 groups. (5) Punctual or streaky haemorrhagia could be found in Gastric mucosa through gross observation, small ulcer was found occasionally. In HE staining sections, there was no gastric mucosa damage in FO group, however, gastric mucosa integrity destruction; parts of mucosa cells necrosis; nucleus extinction; submucous haemorrhagia; blood vessel expansion; blood congestion were found in other 3 groups. In ABPAS staining sections, there was no abnormality in FO group, pathologic changes were found in other 3 groups including covering epithelium integrity destruction; various mucus cells increase; gland expansion and so on. In hybridization in situ sections, there were no iNOS positive cells in FO group, iNOS positive cells were found in other 3 groups in mucous layer , tela submucosa and vascular wall. CONCLUSION: (1) Increase in gastric mucosa damage index and significant increase in stress state in obstructive<WP=7>jaundice rats suggested that stomach damage factors increase obviously in obstructive jaundice. (2) The obvious increase in plasma NO and iNOS of tissue of stomach are the reason leading to acute gastric mucosa pathological change in obstructive jaundice and obstructive jaundice stress rats.更多还原