CAJ | 학술논문

目的探讨胆管上皮细胞增殖及其转分化在肝纤维化形成过程中的作用及黄芪汤组分抑制肝纤维化的效应和机制.方法 30只SD雄性大鼠采用胆总管结扎制备胆汁淤积性肝纤维化模型,假手术对照组仅对胆总管作分离,不结扎.胆管结扎术后l周随机分为模型对照组和药物干预组(经灌胃给予黄芪汤组分4周),5周后麻醉下处死大鼠,获取肝组织与血清标本.检测肝功能、肝组织学及羟脯氨酸(Hyp)含量;激光共聚焦显微镜观察肝组织角蛋白-7(CK7)与α-平滑肌肌动蛋白(α-SMA)共定位,Western blot检测CK7、α-SMA蛋白表达.计量资料比较采用单因素方差分析中的LSD法或非参数检验中的H检验进行统计学分析,计数资料采用Radit检验,CK7与α-SMA蛋白表达间关系采用直线回归与相关分析.结果与假手术对照组比较,模型对照组大鼠病死率33.3%,腹水出现率90%,肝功能显著异常,肝组织肝细胞显著减少,胆管上皮细胞及纤维组织大量增生,肝组织Hyp含量、CK7及α-SMA蛋白表达显著增加(P值均<0.01),并有大量的CK7及α-SMA共定位阳性细胞表达.与模型对照组比较,药物干预组大鼠病死率、腹水出现率及脾脏质量均显著降低(P值均<0.05),肝功能显著改善,肝组织肝细胞减少及胆管上皮细胞与纤维增生程度轻,CK7与α-SMA共定位阳性细胞显著减少.药物干预组与模型对照组大鼠肝Hyp含量分别为(1026.8±132.47)μg/g和(887.4±95.56)μg/g,CK7表达量分别为0.812±0.298和0.318±0.143,α-SMA蛋白表达量分别为0.787±0.277和0.341±0.119,差异均有统计学意义(JD值均<0.01).结论黄芪汤组分可有效抑制胆管结扎大鼠胆管上皮细胞增生及胆管上皮细胞向α-SMA阳性的肌成纤维细胞的转分化.
목적 탐토담관상피세포증식급기전분화재간섬유화형성과정중적작용급황기탕조분억제간섬유화적효응화궤제.방법 30지SD웅성대서채용담총관결찰제비담즙어적성간섬유화모형,가수술대조조부대담총관작분리,불결찰.담관결찰술후l주수궤분위모형대조조화약물간예조(경관위급여황기탕조분4주),5주후마취하처사대서,획취간조직여혈청표본.검측간공능、간조직학급간포안산(Hyp)함량;격광공취초현미경관찰간조직각단백-7(CK7)여α-평활기기동단백(α-SMA)공정위,Western blot검측CK7、α-SMA단백표체.계량자료비교채용단인소방차분석중적LSD법혹비삼수검험중적H검험진행통계학분석,계수자료채용Radit검험,CK7여α-SMA단백표체간관계채용직선회귀여상관분석.결과 여가수술대조조비교,모형대조조대서병사솔33.3%,복수출현솔90%,간공능현저이상,간조직간세포현저감소,담관상피세포급섬유조직대량증생,간조직Hyp함량、CK7급α-SMA단백표체현저증가(P치균<0.01),병유대량적CK7급α-SMA공정위양성세포표체.여모형대조조비교,약물간예조대서병사솔、복수출현솔급비장질량균현저강저(P치균<0.05),간공능현저개선,간조직간세포감소급담관상피세포여섬유증생정도경,CK7여α-SMA공정위양성세포현저감소.약물간예조여모형대조조대서간Hyp함량분별위(1026.8±132.47)μg/g화(887.4±95.56)μg/g,CK7표체량분별위0.812±0.298화0.318±0.143,α-SMA단백표체량분별위0.787±0.277화0.341±0.119,차이균유통계학의의(JD치균<0.01).결론 황기탕조분가유효억제담관결찰대서담관상피세포증생급담관상피세포향α-SMA양성적기성섬유세포적전분화.
Objective To elucidate the antifibrotic mechanism of Huangqi decoction in rats with BDL-induced cholestatic liver fibrosis. Methods Liver fibrosis model was induced by ligating the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly devided into two groups: the BDL group and the Huangqi decoction group. Huanqi decoction was given intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed. Results Compared with the sham control group, mortality rate in BDL group was 33.3% and incidence rate of ascites was 90%, and hepatic function was abnormal in most of the rats in BDL group. The number of Hepatocytes was decreased and the number of cholangiocytes significantly increased in BDL group. In addition, Hyp content of liver tissue and protein expression of CK 7 and α -SMA were significantly increased. Immunostaining indicated that CK 7 and α -SMA were co-localized in BDL group. These changes were markedly suppressed by the Huangqi decoction. Conclusions These observations suggest that Huangqi decoction can inhibit cholangiocyte proliferation and cholangiocyte transdifferentiation.