摘要
目的研究败黄肝宁合剂对α-萘异硫氰酸酯(ANIT)诱导的淤胆型肝炎模型小鼠的治疗作用,探讨败黄肝宁合剂改善淤胆型肝炎的机制。方法雄性小鼠60只,随机分为正常对照组,模型对照组,熊去氧胆酸组及败黄肝宁合剂小、中、大剂量组,每组10只。采用ANIT(60 mg·kg^(-1))诱导制作小鼠淤胆型肝炎模型。检测小鼠胆汁流量、血清生化相关指标、肝组织病理形态学、肝组织生化指标及转化生长因子(TGF)β_(1)、P-Smad2及P-Smad3蛋白的表达。结果与模型对照组比较,败黄肝宁合剂大、中剂量组血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(T-BiL)、直接胆红素(D-BiL)、碱性磷酸酶(ALP)、总胆汁酸(TBA)均显著降低(均P<0.01),胆汁流量显著升高(P<0.01),败黄肝宁合剂小剂量组变化不明显;病理组织学观察结果显示,与模型对照组比较,败黄肝宁合剂大、中剂量组胆管损伤、胆汁淤积和肝细胞损伤显著减轻。与熊去氧胆酸组比较,败黄肝宁合剂大、中剂量组丙二醛(MDA)及一氧化氮(NO)水平均显著降低,肝组织Na^(+)-K^(+)-ATP酶、超氧化物歧化酶(SOD)活性升高,TGF-β_(1)、P-Smad2及P-Smad3降低。结论败黄肝宁合剂对ANIT诱导的小鼠淤胆型肝炎有明显的改善作用。败黄肝宁合剂可抑制TGF-β_(1)、P-Smad2以及P-Smad3蛋白表达水平,从而调节胆汁酸代谢,抑制肝星状细胞增殖活化及胶原蛋白合成,延缓淤胆型肝炎的发生。
Objective To study the therapeutic effect of Baihuang Ganning mixture on mice with cholestatic hepatitis model induced byα-naphthalene isothiocyanate(ANIT),and to explore the mechanism by which Baihuang Ganning mixture improves cholestatic hepatitis.Methods A cholestatic hepatitis model was established in mice by intragastric administration of ANIT(60 mg·kg^(-1)).Sixty mice were randomly divided into six groups(n=10):normal control group,model control group,the ursodeoxycholic acid group,and the high,medium,and low-dose of Baihuang Ganning mixture groups.Parameters including bile flow rate,serum biochemical indices(ALT,AST,T-BiL,D-BiL,ALP and TBA),histopathological changes in liver tissue,hepatic biochemical markers(MDA,NO,Na^(+)-K^(+)-ATPase and SOD),and expression levels of TGF-β_(1),P-Smad2,and P-Smad3 were evaluated.Results Serum biochemical analysis revealed that,compared to the model control group,the high and medium-dose Baihuang Ganning mixture groups exhibited significant reductions in ALT,AST,T-BiL,D-BiL,ALP,and TBA levels(P<0.01),along with increased bile flow rate(P<0.01).No significant changes were observed in the low-dose group.Histopathological examination demonstrated that high and medium-dose Baihuang Ganning mixture markedly alleviated ANIT-induced bile duct injury,cholestasis,and hepatocyte injury.Compared to the ursodeoxycholic acid group,high and medium-dose Baihuang Ganning mixture significantly reduced hepatic MDA and NO levels,enhanced Na^(+)-K^(+)-ATPase and SOD activities(P<0.01),and downregulated the expression of TGF-β_(1),P-Smad2,and P-Smad3.Conclusions Baihuang Ganning mixture significantly improved ANIT-induced cholestatic hepatitis in mice.Baihuang Ganning mixture can regulate the metabolism of bile acids,inhibit the proliferation and activation of hepatic stellate cells(HSC)and the synthesis of collagen,and delay the occurrence of cholestatic hepatitis by inhibiting the expression levels of TGF-β_(1),P-Smad2 and P-Smad3 proteins.
作者
杨全伟
黄蕾
田宇
胡松
徐宏峰
YANG Quanwei;HUANG Lei;TIAN Yu;HU Song;XU Hongfeng(Department of Pharmacy,Wuhan No.1 Hospital,Wuhan 430022,China)
出处
《医药导报》
北大核心
2025年第9期1379-1384,共6页
Herald of Medicine
基金
武汉市卫健委中医面上项目(WZ21A01)。
关键词
败黄肝宁合剂
熊去氧胆酸
肝炎
淤胆型
Baihuang Ganning mixture
Ursodeoxycholic acid
Hepatitis,cholestatic
作者简介
杨全伟(1986-),男,山西晋中人,主管药师,硕士,主要从事中药药效作用机制研究。ORCID:0000-0001-8068-7583,电话:027-85332445,E-mail:553657004@qq.com;通信作者:徐宏峰(1979-),男,湖北武汉人,副主任中药师,硕士,主要从事医院药事管理及医院制剂临床前研究。电话:027-61871268,E-mail:282215830@qq.com。
