CAJ | 학술논문

目的探讨发现γ-氨基丁酸B(GABAB)受体对肝纤维化的调控作用.方法 32只SD 大鼠分为4组,每组8只,分别为对照组、模型组、baclofen处理组和CGP35348处理组.用四氯化碳(CCl4)溶液诱导肝纤维化,baclofen和CGP35348处理均在肝纤维化形成后.摘眼球取血测肝功能.留取肝组织标本,分别进行组织学染色、免疫组化、实时PCR和Western blot实验.结果组织学结果显示CGP35348组肝纤维化程度明显重于baclofen组(P＜0.001).baclofen处理组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转氨酶(GGT)、总胆红素(TBil)以及直接胆红素(DBil)血清水平均显著低于CGP35348处理组(P＜0.01).CGP35348处理组ALT、AST、GGT、TBil以及DBil血清水平亦显著高于模型组(P＜0.05).免疫荧光结果提示baclofen处理组肝细胞迁移能力明显抑制.Western blot结果显示baelofen组α-SMA水平显著低于CGP35348组和模型组(P＜0.01).结论本研究首次报道baelofen对肝纤维化的保护作用,可能主要是通过抑制肝细胞的迁移能力而改善肝纤维化.
목적 탐토발현γ-안기정산B(GABAB)수체대간섬유화적조공작용.방법 32지SD 대서분위4조,매조8지,분별위대조조、모형조、baclofen처리조화CGP35348처리조.용사록화탄(CCl4)용액유도간섬유화,baclofen화CGP35348처리균재간섬유화형성후.적안구취혈측간공능.류취간조직표본,분별진행조직학염색、면역조화、실시PCR화Western blot실험.결과 조직학결과현시CGP35348조간섬유화정도명현중우baclofen조(P＜0.001).baclofen처리조병안산전안매(ALT)、천동안산전안매(AST)、γ-곡안선전안매(GGT)、총담홍소(TBil)이급직접담홍소(DBil)혈청수평균현저저우CGP35348처리조(P＜0.01).CGP35348처리조ALT、AST、GGT、TBil이급DBil혈청수평역현저고우모형조(P＜0.05).면역형광결과제시baclofen처리조간세포천이능력명현억제.Western blot결과현시baelofen조α-SMA수평현저저우CGP35348조화모형조(P＜0.01).결론 본연구수차보도baelofen대간섬유화적보호작용,가능주요시통과억제간세포적천이능력이개선간섬유화.
Objective To investigate the role of r-aminobutyric acid B receptor in the development of liver fibrosis.Methods Thirty-two Sprague-Dawley (SD) rats were divided into four groups including a control group,a model group,a baclofen group,and a CGP35348 group.Liver fibrosis was then induced by carbon tetrachloride (CCl4).Baclofen and CGP35348 treatment were carried out after the formation of liver fibrosis,followed by complete extraction of the eyeball to obtain blood sample to test liver function.Liver tissue specimens were cut and stored for histological staining,histochemistry,real-time polymerase chain-reaction (RT-PCR),and western blot analysis.Results Histological staining indicated that the degree of liver fibrosis was more severe in the CGP35348 group than in the baclofen group (P＜0.001).The levels of alanine transaminase (ALT),aspartate aminotransferase (AST),gamma-glutamyl transferase (GGT),total bilirubin (TBil),and direct bilirubin (DBil) were significantly lower in the baclofen group than in the CGP35348 group (P＜0.01).The levels of ALT,AST,GGT,TBil,and DBil were significantly higher in the CGP35348 group than in the model group (P＜0.05).Immunofluorescence results show that the hepatic cell migration was inhibited in the baclofen group.Western blot results showed that the expression levels of α-SMA protein were significantly lowered in the baclofen group when compared to that of the CGP35348 group and model group (P＜0.01).Conclusion GABAB receptor might play a role in the liver protection by inhibition of migration of hepatic cells in liver fibrosis.Further studies into the mechanism behind this function are further needed and may be a potential source of future anti-fibrotic treatment.