CAJ | 학술논문

目的：探讨丹皮酚对大鼠肝纤维化的治疗作用及其机制。方法将33只大鼠随机分为正常组、模型对照组、丹皮酚干预组，每组11只，模型对照组及丹皮酚干预组采用四氯化碳（ CCl4）诱导建立肝纤维化模型。建模结束后，丹皮酚干预组予4000 mg／kg丹皮酚灌胃，正常组及模型对照组予相同容积0．9％氯化钠注射液灌胃。连续灌胃2周后，观察比较3组大鼠体质量、肝质量及肝指数，测定血清肝纤维化生化指标血清Ⅲ型前胶原肽（ PⅢP）、层黏连蛋白（ LN）、Ⅳ型胶原蛋白（ collagens Ⅳ）及透明质酸（ HA）水平，肝组织氧化应激指标超氧化物歧化酶（SOD）、谷胱甘肽转移酶（GST）、谷胱甘肽（GSH）及丙二醛含量（MDA），肝组织病理切片行马松（ Masson）三色染色检测肝纤维化情况，逆转录酶－聚合酶链反应（ RT－PCR）检测collagensⅠmRNA的表达。结果造模后，模型对照组及丹皮酚干预组大鼠体质量均低于正常组，肝质量及肝指数均高于正常组（P＜0．05），但丹皮酚干预组肝指数增加幅度低于模型对照组（P＜0．05）；模型对照组及丹皮酚干预组肝组织Masson染色胶原纤维较正常组均明显增加（P＜0．05），但丹皮酚干预组增加情况低于模型对照组（P＜0．05）；模型对照组及丹皮酚干预组大鼠血清肝纤维化生化指标PⅢP、LN、collagensⅣ及HA水平较正常组均明显增高（P＜0．05），但丹皮酚干预组增加幅度均低于模型对照组（P＜0．05）；模型对照组及丹皮酚干预组collagensⅠmRNA表达较正常组均显著升高（P＜0．05），但丹皮酚干预组collagens Ⅰ mRNA表达增加幅度低于模型对照组（P＜0．05）；模型对照组及丹皮酚干预组大鼠肝组织MDA、GST水平较正常组均显著升高（P＜0．05），GSH、SOD水平均显著降低（P＜0．05），但丹皮酚干预组MDA、GST升高幅度及GSH、SOD降低幅度均低于模型对照组（P＜0．05）。结论丹皮酚可以缓解CCl4诱导的大鼠肝纤维化过程，其作用机制可通过降低氧化应激水平，增强抗氧化作用来改善肝纤维化进程。目的：探討丹皮酚對大鼠肝纖維化的治療作用及其機製。方法將33隻大鼠隨機分為正常組、模型對照組、丹皮酚榦預組，每組11隻，模型對照組及丹皮酚榦預組採用四氯化碳（ CCl4）誘導建立肝纖維化模型。建模結束後，丹皮酚榦預組予4000 mg／kg丹皮酚灌胃，正常組及模型對照組予相同容積0．9％氯化鈉註射液灌胃。連續灌胃2週後，觀察比較3組大鼠體質量、肝質量及肝指數，測定血清肝纖維化生化指標血清Ⅲ型前膠原肽（ PⅢP）、層黏連蛋白（ LN）、Ⅳ型膠原蛋白（ collagens Ⅳ）及透明質痠（ HA）水平，肝組織氧化應激指標超氧化物歧化酶（SOD）、穀胱甘肽轉移酶（GST）、穀胱甘肽（GSH）及丙二醛含量（MDA），肝組織病理切片行馬鬆（ Masson）三色染色檢測肝纖維化情況，逆轉錄酶－聚閤酶鏈反應（ RT－PCR）檢測collagensⅠmRNA的錶達。結果造模後，模型對照組及丹皮酚榦預組大鼠體質量均低于正常組，肝質量及肝指數均高于正常組（P＜0．05），但丹皮酚榦預組肝指數增加幅度低于模型對照組（P＜0．05）；模型對照組及丹皮酚榦預組肝組織Masson染色膠原纖維較正常組均明顯增加（P＜0．05），但丹皮酚榦預組增加情況低于模型對照組（P＜0．05）；模型對照組及丹皮酚榦預組大鼠血清肝纖維化生化指標PⅢP、LN、collagensⅣ及HA水平較正常組均明顯增高（P＜0．05），但丹皮酚榦預組增加幅度均低于模型對照組（P＜0．05）；模型對照組及丹皮酚榦預組collagensⅠmRNA錶達較正常組均顯著升高（P＜0．05），但丹皮酚榦預組collagens Ⅰ mRNA錶達增加幅度低于模型對照組（P＜0．05）；模型對照組及丹皮酚榦預組大鼠肝組織MDA、GST水平較正常組均顯著升高（P＜0．05），GSH、SOD水平均顯著降低（P＜0．05），但丹皮酚榦預組MDA、GST升高幅度及GSH、SOD降低幅度均低于模型對照組（P＜0．05）。結論丹皮酚可以緩解CCl4誘導的大鼠肝纖維化過程，其作用機製可通過降低氧化應激水平，增彊抗氧化作用來改善肝纖維化進程。
목적：탐토단피분대대서간섬유화적치료작용급기궤제。방법장33지대서수궤분위정상조、모형대조조、단피분간예조，매조11지，모형대조조급단피분간예조채용사록화탄（ CCl4）유도건립간섬유화모형。건모결속후，단피분간예조여4000 mg／kg단피분관위，정상조급모형대조조여상동용적0．9％록화납주사액관위。련속관위2주후，관찰비교3조대서체질량、간질량급간지수，측정혈청간섬유화생화지표혈청Ⅲ형전효원태（ PⅢP）、층점련단백（ LN）、Ⅳ형효원단백（ collagens Ⅳ）급투명질산（ HA）수평，간조직양화응격지표초양화물기화매（SOD）、곡광감태전이매（GST）、곡광감태（GSH）급병이철함량（MDA），간조직병리절편행마송（ Masson）삼색염색검측간섬유화정황，역전록매－취합매련반응（ RT－PCR）검측collagensⅠmRNA적표체。결과조모후，모형대조조급단피분간예조대서체질량균저우정상조，간질량급간지수균고우정상조（P＜0．05），단단피분간예조간지수증가폭도저우모형대조조（P＜0．05）；모형대조조급단피분간예조간조직Masson염색효원섬유교정상조균명현증가（P＜0．05），단단피분간예조증가정황저우모형대조조（P＜0．05）；모형대조조급단피분간예조대서혈청간섬유화생화지표PⅢP、LN、collagensⅣ급HA수평교정상조균명현증고（P＜0．05），단단피분간예조증가폭도균저우모형대조조（P＜0．05）；모형대조조급단피분간예조collagensⅠmRNA표체교정상조균현저승고（P＜0．05），단단피분간예조collagens Ⅰ mRNA표체증가폭도저우모형대조조（P＜0．05）；모형대조조급단피분간예조대서간조직MDA、GST수평교정상조균현저승고（P＜0．05），GSH、SOD수평균현저강저（P＜0．05），단단피분간예조MDA、GST승고폭도급GSH、SOD강저폭도균저우모형대조조（P＜0．05）。결론단피분가이완해CCl4유도적대서간섬유화과정，기작용궤제가통과강저양화응격수평，증강항양화작용래개선간섬유화진정。
Objective To study the therapeutic effects and mechanism of paeonol on hepatic fibrosis rats. Methods 33 rats were randomly divided into normal group, model group and paeonol intervention group, 11 rats in each group.Liver Fibrosis model in model group and paeonol intervention group were induced by carbon tetrachloride ( CCl4 ) .After modeling, rats in paeonol intervention group received paeonol (4 000 mg/kg) via gastrogavage, rats in other two groups received 0.9%sodium chloride injection via gastrogavage at the same dose.After 8 weeks of gastric perfusion, the level of body mass, liver mass and liver index in rats were observed in three groups.The level of the serum liver fibrosis biochemical index like serum procollagen typeⅢpeptide ( PⅢP) , laminin lens ( LN) , collagensⅣand hyaluronic acid ( HA ) , and the degree of the liver tissue oxidative stress index like superoxide dismutase ( SOD) , glutathione-transferase ( GST) , glutathione ( GSH) and malondialdehyde content ( MDA) were detected in three groups, the liver fibrosis degree of liver tissue pathological section was detected by masson's trichrome stai-ning, and the expression of collagensⅠmRNA was detected by inverse transcriptase-polymerase chain reaction ( RT-PCR) .Results After modeling, the level of rats body mass in model group and paeonol intervention group was lower than that in normal group (P<0.05), the level of liver mass and liver index were increased (P<0.05), but the increase of liver index in paeonol intervention group was lower than that in model group (P<0.05).Masson's staining collagen fiber of liver tissue in model group and paeonol intervention group was significantly increased as compared with that in normal group (P<0.05), but the in-crease in paeonol intervention group was lower than that in model group (P<0.05).The degree of PⅢP, LN, colla-gens Ⅳand HA in model group and paeonol intervention group were significantly increased as compared with those in normal group (P<0.05), but the increase in paeonol intervention group was lower than that in model group (P<0.05).The expression of collagensⅠmRNA in model group and paeonol intervention group was significantly increased as compared with that in normal group(P<0.05), the increase in paeonol intervention group was lower than that in model group (P<0.05).The level of MDA, GST of rats liver tissue in model group and paeonol intervention group were significantly increased as compared with those in normal group (P<0.05), the level of GSH, SOD were de-creased (P<0.05), but the change range in paeonol intervention group was smaller than that in model group (P<0.05).Conclusion Paeonol can relief carbon tetrachloride-induced liver fibrosis degree in rats through the action mechanism of decreasing oxidative stress level and enhance antioxidation effect.