摘要
目的:探讨骨化三醇对胆总管结扎(BDL)诱导的小鼠肝纤维化的保护作用,并阐述其可能的作用机制。方法:选用45只8~10周雄性C57BL/6小鼠,随机分为假手术组、肝纤维化模型组(模型组)和骨化三醇治疗组(治疗组),每组15只。假手术组小鼠绕胆总管穿过手术线,不结扎。模型组小鼠双重结扎胆总管并离断。治疗组小鼠术后2.5μg·kg~(-1)腹腔注射骨化三醇,每周3次。假手术组和模型组小鼠注射等体积生理盐水。术后继续给药4周,第28天眼眶取血,取小鼠肝脏。术后第2天检测各组小鼠血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性及总胆汁酸(TBA)、总胆红素(TBIL)和羟脯氨酸(Hyp)水平。苏木精-伊红(HE)染色和天狼猩红染色观察各组小鼠肝组织病理形态学和肝组织纤维化程度。Western blotting法检测各组小鼠肝组织中维生素D受体(VDR)细胞外信号调节蛋白激酶(ERK)、磷酸化细胞外信号调节蛋白激酶(p-ERK)、α-平滑肌蛋白(α-SMA)、转化生长因子β1 (TGF-β1)、Ⅰ型胶原蛋白(ColⅠ)和结蛋白(Desmin)表达水平。免疫组织化学法检测各组小鼠肝组织中α-SMA和TGF-β1蛋白表达情况。结结果果:与假手术组比较,模型组小鼠血清中ALT和AST活性及TBA、TBIL和Hyp水平明显升高(P<0.05);与模型组比较,治疗组小鼠血清中ALT和AST活性及TBA、TBIL和Hyp水平明显降低(P<0.05)。HE染色,假手术组小鼠肝小叶正常,组织结构较为完整,未见炎性细胞浸润;模型组小鼠肝组织出现炎性细胞浸润,坏死灶和胶原沉积较为明显;与模型组比较,治疗组小鼠肝组织坏死灶区域明显减少,炎性浸润有所改善。天狼猩红染色,假手术组小鼠肝组织仅有少量胶原沉积出现在中央静脉周围;模型组小鼠肝组织中央静脉及汇管区出现明显胶原沉积;与模型组比较,治疗组胶原沉积明显减少。Western blotting法检测,与假手术组比较,模型组�
Objective:To investigate the protective effect of calcitriol on liver fibrosis induced by common bile duct ligation(BDL)in the mice,and to explain its possible mechanism.Methods:Forty-five male C57BL/6 mice aged 8 to 10 weeks were randomly divided into sham operation group,liver fibrosis model group(model group)and calcitriol treatment group(treatment group),with 15 mice in each group.The mice in sham operation group received the surgical line around the common bile duct without ligation;in model group,the common bile ducts of the mice were double-ligated and severed,and the mice in treatment group were injected intraperitoneally with calcitriol(2.5μg·kg-1)3 times a week after operation.The mice in sham operation group and model group were injected with an equal volume of saline.The administration was continued until 4 weeks after the operation.On the 28 th day,blood was taken from the orbit and the liver of the mouse was taken.On the second day after the operation,the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)and the levels of total bile acid(TBA),total bilirubin(TBIL)and hydroxyproline(Hyp)in the serum of the mice in various groups were detected.The pathomorphology and fibrosis degrees of liver tissue were observed with hematoxylin and eosin(HE)and Sirius red staining.Western blotting method was used to detect the expression levels of vitamin D receptor(VDR),extracellular signal-regulated protein kinase(ERK),phosphorylated extracellular signal-regulated protein kinase(pERK),α-smooth muscle protein(α-SMA),transforming growth factor-β1(TGF-β1),typeⅠcollagen(ColⅠ)and Desmin in liver tissue of the mice in various groups.Immunohistochemistry method was used to detect the expressions ofα-SMA and TGF-β1 in liver tissue of the mice in various groups.Results:Compared with sham operation group,the serum activities of ALT and AST and the levels of TBA,TBIL and Hyp of the mice in model group were significantly increased(P<0.05);compared with model group,the serum activities o
作者
贾荣军
马丽曼
李丽华
JIA Rongjun;MA Liman;LI Lihua(Department of Cell Biology,School of Basic Medical Sciences,Jinzhou Medical University,Jinzhou 121000,China;Department of Clinical Medicine,School of Medical Sciences,Taizhou University,Taizhou 31800,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2021年第2期257-264,共8页
Journal of Jilin University：Medicine Edition
基金
国家自然科学基金面上项目(31571184)。
