γ-氨基丁酸对溃疡性结肠炎大鼠离体结肠平滑肌的影响  

Effect of γ-aminobutyric acid on isolated colonic smooth muscle from rats with experimental ulcerative colitis

作　　者：鲁兵[1] 余万桂[2] 鄢进[2] 吴国栋[3] 李龙[1] 

机构地区：[1]长江大学医学院,内科学专业湖北省荆州市434023 [2]长江大学医学院医学机能学部,湖北省荆州市434023 [3]荆州市第二人民医院肝病内科,湖北省荆州市434000

出　　处：《世界华人消化杂志》2014年第32期4907-4914,共8页World Chinese Journal of Digestology

基　　金：湖北省自然科学基金资助项目;No.2010CDB04405~~

摘　　要：目的:以硫酸葡聚糖5000(dextran sulfate sodium3%D S S)诱导建立溃疡性结肠炎(u n c r e a t i v e colitis,UC)模型,研究γ-氨基丁酸(γ-aminobutyric acid,GABA)对实验性UC大鼠结肠离体平滑肌的影响.方法:Wistar大鼠17只随机分为正常组(6只)和模型组(11只).正常组饮用蒸馏水,模型组饮用含3%DSS的蒸馏水,诱导建立大鼠UC模型每天观察大鼠体质量和大便性状,进行疾病活动指数(disease activity index,DAI)评分,9 d后模型组UC模型建立.所有大鼠处死后观察大体形态改变,并自病变严重部位取组织标本HE染色,镜下观察结肠的病理学改变.同时取大鼠结肠平滑肌,以离体结肠收缩张力变化为指标观察,观察GABA、GABA A受体激动剂蝇蕈醇和GABA A受体拮抗剂荷包牡丹碱、GABA B受体拮抗剂巴氯酚对大鼠离体结肠平滑肌的影响.结果:模型组大鼠第5天出现大便形状改变30%为大便松散不成型,70%出现腹泻,为黄色稀便,第7天左右40%左右大鼠出现明显血便,活动及进食明显减少,病理学检查正常组大鼠结肠无黏连,黏膜轻度充血,无溃疡形成,镜下组织结构可见,腺体排列基本整齐;模型组大鼠腺体数目减少,组织结构紊乱,黏膜糜烂,出血、坏死和大面积深层溃疡.与正常组相比,模型组大鼠DAI(3.83±2.74 vs1.23±1.62,P<0.05),组织病理学评分(2.52±1.36 v s 0.41±0.74,P<0.05)显著升高;与加GABA前比较,GABA对正常大鼠和UC大鼠离体结肠平滑肌自主收缩活动均有抑制作用(P<0.05),0.01 mmol/L GABA和100 mmol/L G A B A对正常大鼠离体结肠平滑肌抑制率分别为20.00%±0.02%和67.60%±0.03%,0.01 mmol/L GABA和100 mmol/L GABA对溃疡性结肠大鼠离体结肠平滑肌抑制率分别为19.50%±0.02%和64.50%±0.05%,但G A B A对正常大鼠和U C大鼠离体结肠平滑肌自主收缩活动抑制作用差异无统计学意义(P>0.05).与加药前比较,0.01 mmol/L GABA A受体拮抗剂荷包牡丹碱能使大鼠离体结肠平滑肌收缩张力增�AIM： To assess the effect of γ-aminobutyric acid （GABA） on isolated colonic smooth muscle from rats with experimental ulcerative colitis （UC）. METHODS： Seventeen Wistar rats were ran- domly divided into either a normal group （six rats） or a model group （eleven rats）. The nor- mal group was given distilled water, while the model group was given distilled water contain-ing 3% dextran sulfate 5000. The body mass of the rats and the character of the stool were ob- served every day, and the disease active index （DIA） was scored. Nine days later, all the rats were killed to observe the changes of the gross morphology and the pathologic changes of the colon under a microscope by taking tissue spec- imens from serious lesion sites for HE staining. Meanwhile, colonic smooth muscle was isolat- ed to observe the effect of muscimol, a receptor agonist of the GABA and GABAA, bicuculline, an antagonist of the GABAA, and baclofen, a re- ceptor antagonist of the GABAB on the isolated colonic smooth muscle using isometric tension as an indicator. RESULTS： After four days of treatment with dextran sulfate 5000, the character of the stool of rats in the model group changed, with 30% of rats showing loose stool and 70% showing diarrhea. After six days, about 40% of rats had obvious bloody stool and an obvious decrease in activity and eating. In rats of the normal group, gross pathological examination revealed that the colon had no adhesion, the mucosa had mild hyperemia but no ulcers; microscopic pathologi- cal examination revealed intact tissue structure and regularly arranged glands. In rats of the model group, the number of glands decreased, the tissue structure was disorderly, the mucosa was erosive, bleeding, necrotic, and had large deep ulcers. Compared with the normal group, the DIA （3.83 ± 2.74 vs 1.23 ± 1.62, P 〈 0.05） and histopathologic score （2.52 ± 1.36 vs 0.41 ± 0.74, P 〈 0.05） were increased significantly in the model group. Treatment with GABA significantly in- hibited the i

关 键 词：Γ-氨基丁酸 受体激动剂 受体拮抗剂 溃疡结肠炎 结肠离体平滑肌 

分 类 号：R574.62[医药卫生—消化系统]