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1、不同治则中药复方对胆汁淤积性肝纤维化大鼠尿激酶型纤溶酶原激活剂的影响【摘要】目的观察补益肝肾、活血化瘀方二至丸、失笑散及其合方对胆汁淤积性肝纤维化大鼠肝组织尿激酶型纤溶酶原激活剂(uPA)的影响。方法采用胆管结扎复制胆汁淤积性肝纤维化大鼠模型。造模大鼠于术后1周随机分为模型组、优思弗组、二至丸组、失笑散组及合方组;各药物干预组分别给予相应药物灌胃,模型组和假手术组给予等量生理盐水灌胃,至4周末处死全部动物取材。观察各组大鼠一般情况、肝功能(ALT、AST、ALP、TBil)、肝组织病理、uPA蛋白表达(Westernblot法)。结果与假手术组比较,模型组大鼠ALT、AST、ALP、TBil
2、、纤维化程度均显著升高。与模型组比较,3个复方均能降低大鼠血清ALP、ALT、AST水平(P<0.01),失笑散及合方能降低TBil(P<0.01),合方改善ALP、ALT优于两个单方。3个复方均能不同程度地减轻模型大鼠肝纤维化程度(P<0.01),合方优于两个单方。优思弗能降低ALT、AST水平,但对肝脏纤维化无明显改善作用。与模型组比较,3个复方组uPA蛋白表达显著增加(P<0.01),其中合方组最高,失笑散组次之,再次为二至丸组,三者之间比较差异有统计学意义(P<0.05,P<0.01)。结论二至丸、失笑散及其合方均可不同程度地干预胆汁淤积性肝纤维化形成,其机制可能与调控uPA蛋白表达
3、有关。【关键词】胆汁淤积性肝纤维化;二至丸;失笑散;尿激酶型纤溶酶原激活剂;Western印迹;大鼠13Abstract:ObjectiveTostudytheeffectsoftheChineseherbalcompound(Erzhiwan,Shixiaosanandcombinedformula)oncholestasis-inducedliverfibrosisrat’suPA.MethodsBileductligationmethodwasusedtomakethemodelofcholestasis-inducedliverfibrosis.Oneweekaftertheoper
4、ation,theratswererandomlydividedintofivegroup(modelgroup,UDCAgroup,Erzhiwangroup,Shixiaosangroupandhefanggroup).Eachmedicineinterventiongroupwasgivencorrespondingmedicinebyintragastricadministration.Shamandmodelgroupweregivensodiumchloridewithequaldosage.Attheendof4thweek,allratsweresacrificedandsa
5、mpled.Generalstateofhealth,hepaticfunction(ALT,AST,ALP,TBil)andpathologicalhistologyofhepatictissuewererecordedandmeasured.ResultsComparedwiththeshamgroup,thelevelofALT,AST,ALP,TBilandthedegreeofliverfibrosisinmodelgroupwereadvancedsignificantly.Comparedwithmodelgroup,threeChineseherbalcompounddecr
6、easedserumlevelofALP,ALTandAST(P<0.01).ShixiaosanandhefangdecreasedserumlevelofTBil(P<0.01).HefangwasbetterthansimplerecipeonALPandALT.Threeherbalcompoundreleasedliverfibrosistosomeextent(P<0.01),andhefangwasbetterthansimplerecipe.UDCA13decreasedserumlevelofALTandAST,buthadnoeffectonliverfibrosis.C
7、omparedwithmodelgroup,uPAexpressionsignificantlyincreasedinthreeChineseherbalgroups(P<0.01),andhefanggroupwasthehighest,Shixiaosangroupwasthemiddle,Erzhiwangroupwasthelowest.ConclusionChineseherbalcompound(