氧化苦参碱对慢性胰腺炎胰腺组织中Ⅰ型胶原及α-SMA的影响  

Oxymatrine enhances the expression of collagen I and α-SMA in rat chronic pancreatitis

作　　者：王昱良[1] 郑永青 夏时海[3] 汪海燕 苏丽婷[3] 吴双[3] 

机构地区：[1]河南省三门峡市黄河医院消化内科,河南省三门峡市472000 [2]武警8650部队医院内科,山西省晋中市030600 [3]天津市武警医学院附属医院肝胆胰脾内科,天津市300162

出　　处：《世界华人消化杂志》2010年第13期1331-1336,共6页World Chinese Journal of Digestology

基　　金：武警总部自然科学基金资助项目;No.WKH2006-9~~

摘　　要：目的:探讨氧化苦参碱对大鼠慢性胰腺炎的治疗作用及其机制.方法:Wistar大鼠40只,按照随机数字表分为:阴性对照组(NC组,n=10),以300mg/kg隔日腹腔内注射生理盐水;模型组(CP组,n=10),以700mg/kg隔日腹腔内注射二乙基二硫代氨基甲酸钠(DDC);OM治疗组(OT组,n=10),以700mg/kg隔日腹腔内注射DDC,1wk后开始每日腹腔注射OM100mg/kg;OM预防组(OP组,n=10),依照模型组方法注射DDC的同时每日腹腔内注射OM100mg/kg.到30d时停止注射DDC,但仍继续注射OM.将上述4组分别在20d、40d处死大鼠(n=5),用Masson染色的方法观察胶原纤维增生,用免疫组织化学的方法观察Ⅰ型胶原、α-SMA在胰腺组织的定位及表达,用Westernblot方法检测α-SMA在胰腺组织表达量的变化.结果:Masson染色可见胶原纤维面积百分比,分别在20、40d时CP组(22.54%±4.45%、35.14%±3.27%)高于其余各组(P<0.05),OP组(13.16%±1.84%、25.14%±3.67%)与OT组(19.58%±2.78%、28.68%±2.55%)较CP组降低(P<0.05),NC组(3.0%±0.32%、2.45%±0.24%)低于其余各组(P<0.05),CP组与OT组在40d时的胶原纤维面积百分比较20d时增高(P<0.05).Ⅰ型胶原与α-SMA在胰腺组织的定位:用免疫组织化学的方法发现NC组胰腺组织α-SMA在血管壁平滑肌表达阳性,其余部位未见表达;CP组α-SMA在血管周围和腺泡间有阳性表达;在OT、OP组,α-SMA在腺泡间有少量表达.Ⅰ型胶原在NC组主要位于胰腺组织周边;CP组除在上述部位外,还表达于腺泡间及小叶周围.用Westernblot方法检测胰腺组织中α-SMA与β-actin的相对表达量分别在20、40d时CP组(1.06±0.04、1.16±0.03)高于其余各组(P<0.05),NC组(0.73±0.06、0.78±0.06)低于其余各组(P<0.05),OT组与OP组比较无差别(P>0.05).结论:慢性胰腺炎时Ⅰ型胶原和α-SMA表达增强,主要位于血管和腺泡周围以及小叶间.OM可以通过减少胰腺组织内胶原的生成及PSC的活化抑制胰腺纤维化的发展.AIM：To investigate the treatment effects of oxymatrine （OM） against chronic pancreatitis in rats and to explore the potential mechanisms involved.METHODS：Forty healthy Wistar rats were randomly and equally divided into four groups：negative control group （NC group）,CP model group （CP group）,OM treatment group （OT group）,and OM pretreatment group （OP group）,which received saline qod,diethyldithiocarbamate （DDC） at 700 mg/kg qod,diethyldithiocar-bamate （DDC） at 700 mg/kg qod and OM at 100 mg/kg a week later,and diethyldithiocarbamate （DDC） at 700 mg/kg qod and OM at 100 mg/kg simultaneously,respectively. Thirty days later,DDC injection was discontinued,while OM treatment continued. Rats were executed on days 20 and 40 （n = 5 at each time point）. Collagen fibers were stained by Masson＇s trichrome. The localization and expression of collagen I and α-SMA in chronic pancreatitis were examined by immunohistochemistry. RESULTS：Collage I was localized in the periphery of the pancreas in the NC group. In the CP group,collagen I could also be seen in periacinar and perilobular areas. The immunoreactivity of α-SMA was detected in the blood vessel wall in the NC group,and in the blood vessel wall and periacinar area in the CP group. The expression of collagen I and α-SMA in periacinar area was significantly lower in the OP and OT groups than in the CP group. The percentages of collagen area on days 20 and 40 were significantly lower in the NC group （3.0% ± 0.32% and 2.45% ± 0.24%） than in the other groups （all P 0.05）,but significantly higher in the CP group （22.54% ± 4.45% and 35.14% ± 3.27%） than in the OP group （13.16% ± 1.84% and 25.14% ± 3.67%） and the OT group （19.58% ± 2.78% and 28.68% ± 2.55%）. The percentages of collagen areas on day 40 in the CP and OT groups were significantly higher than those on day 20 （both P 0.05）. The relative expression levels of α-SMA on days 20 and 40 were significantly higher in the CP group （1.06 ± 0.04 an

关 键 词：胰腺纤维化 慢性胰腺炎 氧化苦参碱 Ⅰ型胶原 α-平滑肌肌动蛋白 

分 类 号：R285.5[医药卫生—中药学]