CAJ | 학술논문

目的：通过观察柴胡疏肝散对二氯二丁基酯（ DBTC）联合乙醇所致慢性胰腺炎小鼠胰腺丙二醛（ MDA）和超氧化物歧化酶（ SOD）的影响，探讨柴胡疏肝散防治胰腺纤维化的机制。方法：健康昆明小鼠120只随机分为空白组、模型组和柴胡疏肝散治疗组（n＝40）。除空白组外，其余小鼠经尾静脉一次性注射DBTC（8 mg/kg）后，联合饮用10％乙醇诱发慢性胰腺炎。造模后3 d 治疗组小鼠给予柴胡疏肝散（6 g· kg－1· d－1）灌胃，空白组和模型组给予生理盐水灌胃。于造模前及造模后1、2、4、8周分批处死小鼠，HE染色检测各组小鼠胰腺组织的形态学改变及纤维化程度；化学比色法和ELISA法分别检测血清淀粉酶和透明质酸的变化；酶化学法检测胰腺组织匀浆SOD和MDA的水平；Western blotting检测胰腺组织Ⅰ型胶原的表达。结果：DBTC联合饮用乙醇2周和4周血清淀粉酶及透明质酸处于较高水平，8周时淀粉酶明显降低，而透明质酸水平进一步升高，各指标与相应时点空白组相比有显著差异（ P＜0．05）。造模后2、4、8周胰腺组织匀浆MDA 的水平持续升高，SOD活性持续降低，与相应时点空白组相比有显著差异（P＜0．05）；造模后1周胰腺实质肿胀、坏死，2周可见小叶间纤维化。造模4周和8周显示胰腺腺泡明显萎缩，出现典型、广泛的不规则纤维化，胰腺Ⅰ型胶原的表达亦呈现较高水平。柴胡疏肝散治疗后，血清淀粉酶活性和透明质酸含量降低，胰腺组织匀浆MDA的水平降低，SOD活性升高，各时点胰腺的纤维化损伤程度明显减轻。结论：柴胡疏肝散通过抗氧化机制，发挥防治慢性胰腺炎胰腺纤维化的作用。
목적：통과관찰시호소간산대이록이정기지（ DBTC）연합을순소치만성이선염소서이선병이철（ MDA）화초양화물기화매（ SOD）적영향，탐토시호소간산방치이선섬유화적궤제。방법：건강곤명소서120지수궤분위공백조、모형조화시호소간산치료조（n＝40）。제공백조외，기여소서경미정맥일차성주사DBTC（8 mg/kg）후，연합음용10％을순유발만성이선염。조모후3 d 치료조소서급여시호소간산（6 g· kg－1· d－1）관위，공백조화모형조급여생리염수관위。우조모전급조모후1、2、4、8주분비처사소서，HE염색검측각조소서이선조직적형태학개변급섬유화정도；화학비색법화ELISA법분별검측혈청정분매화투명질산적변화；매화학법검측이선조직균장SOD화MDA적수평；Western blotting검측이선조직Ⅰ형효원적표체。결과：DBTC연합음용을순2주화4주혈청정분매급투명질산처우교고수평，8주시정분매명현강저，이투명질산수평진일보승고，각지표여상응시점공백조상비유현저차이（ P＜0．05）。조모후2、4、8주이선조직균장MDA 적수평지속승고，SOD활성지속강저，여상응시점공백조상비유현저차이（P＜0．05）；조모후1주이선실질종창、배사，2주가견소협간섬유화。조모4주화8주현시이선선포명현위축，출현전형、엄범적불규칙섬유화，이선Ⅰ형효원적표체역정현교고수평。시호소간산치료후，혈청정분매활성화투명질산함량강저，이선조직균장MDA적수평강저，SOD활성승고，각시점이선적섬유화손상정도명현감경。결론：시호소간산통과항양화궤제，발휘방치만성이선염이선섬유화적작용。
[ ABSTRACT] AIM:To explore the role of superoxide dismutase ( SOD) and malondialdehyde ( MDA) in chronic pancreatitis ( CP) induced by dibutyltin dichloride ( DBTC) combined with ethanol, and the mechanisms for prevention and treatment of pancreatic fibrosis by Chaihushugansan.METHODS: The KM mice were randomly divided into control group, CP group ( DBTC combined with ethanol) and Chaihushugansan group ( CP+Chaihushugansan) .Except for control group, the mice in other groups were intravenously injected in tail with DBTC (8 mg/kg) and drank 10% ethanol.The mice in Chaihushugansan group were administered intragastrically with Chaihushugansan (6 g· kg-1 · d-1 ) at the follow-ing experimenal period.Before modeling and 1 week, 2 weeks, 4 weeks and 8 weeks after modeling, the mice were anes-thetized and sacrificed.The activity of amylase and the content of hyaluronic acid in the serum were measured.The mor-phology and the degree of fibrosis in the pancreas were observed by HE staining.The activity of SOD and the level of MDA in the pancreas homogenate were analyzed.The protein of pancreas was extracted to detect the expression of type I collagen by Western blotting.RESULTS:DBTC combined with ethanol induced CP with increased serum amylase and hyaluronic acid levels, while the serum amylase and hyaluronic acid levels in Chaihushugansan group were significantly lowered ( P<0.05).In 1 week, 2 weeks, 4 weeks and 8 weeks, the pancreas were obviously injured and appeared different degrees of fibrosis.The content of MDA and the expression of type I collagen in the increased significantly, but the SOD was de-creased.In Chaihushugansan group, the pathological damage and the degree of fibrosis of the pancreas were improved.The level of MDA and type I collagen expression in the pancreas were significantly reduced, but the SOD was increased.CON-CLUSION:The oxidative stress may take part in the development of CP.Inhibition of oxidative stress in the pancreas is one of the mechanisms that Chaihushugansan attenuates the development of CP.