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学科主题: 临床医学
题名:
TUDCA对溃疡性结肠炎小鼠内质网应激和双氧化酶2表达的研究
作者: 梁君
答辩日期: 2016-05-10
导师: 崔梅花
专业: 内科学
授予单位: 北京大学
授予地点: 北京大学航天临床医学院
学位: 硕士
关键词: 溃疡性结肠炎 ; 内质网应激 ; 双氧化酶2 ; 牛磺熊去氧胆酸
其他题名: Expression of Endoplasmic Reticulum Stress Proteins and Dual Oxidase2 in mouse colitis alleviated by Tauroursodeoxycholate
分类号: R574.62
摘要:

目的  探讨特异性内质网应激抑制剂牛磺熊去氧胆酸(tauroursodeoxycholate, TUDCA)对葡聚糖硫酸钠(dextran sulphate sodium,DSS)诱导的小鼠溃疡性结肠炎的内质网应激(endoplasmic reticulum stress, ERS)蛋白与肠黏膜过氧化氢产生酶双氧化酶2(dual oxidase2,DUOX2)的影响及相互作用。

方法  7周C57BL/6J雄性小鼠适应喂养一周后,随机分为对照组、炎症组、干预组。炎症和干预组饮用2.5% DSS溶液诱导小鼠结肠炎,干预组以500mg/kg的TUDCA灌胃。 8天后处死小鼠,收集结肠做HE和免疫组化染色,Western Blot检测DUOX2及ERS相关蛋白GRP78、ATF6、P-IRE1α/IRE1α、IRE1β、P-PERK/PERK的表达后进行相关性分析。

结果  TUDCA明显减轻了DSS诱导的小鼠结肠炎。Western Blot结果为炎症组GRP78、P-PERK/PERK蛋白及DUOX2均表达升高,分别为(0.49±0.13)、(0.41±0.22)、(0.19±0.07);干预组这三种蛋白表达下降,分别为(0.26±0.15)、(0.19±0.10)、(0.07±0.05);与炎症组相比均P<0.05。对照组分别为(0.26±0.13)、(0.21±0.08)、(0.07±0.05)。其余ERS相关蛋白表达无变化(P>0.05)。免疫组化结果GRP78和DUOX2三组表达水平分别与Western Blot结果相一致。炎症组GRP78和DUOX2表达分别为(4.90±1.77)、(5.14±1.50),干预组为(2.32±0.50)、(2.42±0.57), (组间均P<0.05),对照组为(1.49±0.29)、(1.34±0.20)。统计分析结果显示DUOX2蛋白与PERK蛋白的表达有相关性(P<0.05),相关系数为0.349。

结论  TUDCA可以缓解小鼠溃疡性结肠炎的发病程度,GRP78-PERK通路参与DSS诱导的溃疡性结肠炎,该通路与DUOX2表达相互影响。

英文摘要:

Objective Tauroursodeoxycholate (TUDCA), a specific inhibitor of endoplasmic reticulum stress (ERS),was used to alleviate mouse colitis induced by dextran sulfate sodium(DSS) and  the expression of chaperone proteins of ERS and the dual oxidase2 (DUOX2) in colon tissue was evaluated to explore the interaction between ERS and Duox2 in colitis.

Methods  7-week-old C57BL/6J male mice were divided randomly into control, DSS, TUDCA treatment group. Mice in treatment group and inflammation group were used 2.5%DSS  to induce colitis. Mice in treatment group were received 500mg/kg TUDCA by gavage. on 8th day all the mice were sacrificed, the colon tissue were collected, HE staining was used to evaluate pathology of colon, Western Blot and immunohistochemistry (IHC) were used to Examine the expressions of proteins including DUOX2 and GRP78、ATF6、P-IRE1α/IRE1α、IRE1β、P-PERK/PERK.

Results  Mice colitis induced by DSS was alleviated by TUDCA.  The expression of GRP78、DUOX2、P-PERK/PERK in DSS group was increased, which were separately(0.49±0.13)、(0.41±0.22)、(0.19±0.07).And the expression of these proteins was down to the level of control in treatment mice. which were(0.26±0.15)、(0.19±0.10)、(0.07±0.05).(all P<0.05). The control mice were(0.26±0.13)、(0.21±0.08)、(0.07±0.05). Other proteins was not affected by inflammation or TUDCA .The IHC were consistent with the results of GRP78 and DUOX2 by Western Blot. And the scores of IHC were (4.90±1.77)、(5.14±1.50)in DSS group, (2.32±0.50)、(2.42±0.57)in treatment group(all P<0.05), compared to (1.49±0.29)、(1.34±0.20) in control group. Analysis of statistics showed positive correlation between DUOX2 expression and PERK expression.The correlation coefficient is 0.349.

Conclusion  Mouse colitis could be alleviated by TUDCA. GRP78-PERK signal pathway participates in the mouse colitis induced by DSS, there may be interaction between DUOX2 expression and GRP78-PERK signal pathway.

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/125282
Appears in Collections:北京大学航天临床医学院_学位论文

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作者单位: 北京大学航天临床医学院

Recommended Citation:
梁君. TUDCA对溃疡性结肠炎小鼠内质网应激和双氧化酶2表达的研究[D]. 北京大学航天临床医学院. 北京大学. 2016.
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