岩黄连总碱对实验性肝损伤的保护作用及其机制研究
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摘要
目的:研究岩黄连总碱(Corydalis saxicola Bunting Total Alkaloids,CSBTA)对肝脏的保护作用,并探讨其保肝和抗肝纤维化的作用机制。
方法:通过复制四氯化碳(Carbon tetrachloride,CCl4)所致的小鼠急性肝损伤模型观察CSBTA的保肝作用;通过皮下注射四氯化碳,复制大鼠慢性肝纤维化模型,观察CSBTA的抗肝纤维化作用及其可能的作用机制。采用比色法测定ALT、AST、TP、ALB、MDA、SOD、Hyp含量,放射免疫法测定HA、LN含量,小鼠急性肝损伤和大鼠慢性肝纤维化肝组织进行HE染色并在光镜下观察其形态学变化,免疫组织化学染色观察慢性肝纤维化大鼠肝组织TGF-β1和MMP-9的表达情况。
结果: CSBTA可显著地降低大、小鼠血清中的ALT、AST含量(P<0.01, P<0.05),并能显著降低两者肝组织中MDA的水平(P<0.01, P<0.05)升高肝组织中SOD的活性(P<0.01, P<0.05);CSBTA也能降低大鼠肝组织中Hyp的含量(P<0.01, P<0.05)和大鼠血清TP、ALB含量(P<0.01, P<0.05),大鼠血清肝纤维化指标HA、LN也较模型组有明显下降(P<0.01, P<0.05);光镜下CSBTA给药组与模型组比较,可明显减少急性肝损伤时肝组织中的炎症细胞浸润、肝细胞变性和坏死,也可抑制慢性肝纤维化时肝假小叶的形成和胶原纤维沉积(P<0.01, P<0.05);免疫组化显示CSBTA可明显降低由CCl4引起的TGF-β1和MMP-9的升高, CSBTA给药组与模型组比较,两者的表达量明显降低(P<0.01, P<0.05)。
结论:岩黄连总碱对四氯化碳所致急性肝损伤具有明显保护作用,也可抑制大鼠慢性肝纤维化的形成。其机制可能与抗脂质过氧化、抑制胶原蛋白合成,促进细胞外基质降解有关。
OBJECTIVE: To investigate protective effects of Corydalis saxicola Bunting Total Alkaloids(CSBTA) on liver ,and to explore its possible mechanisms of protecting liver and anti-hepatic fibrosis.
METHODS: Animal model of acute liver injury induced by cabron tetrachloride was used to observe the protective effect of CSBTA on liver,model of chronic hepatic fibrosis established by subcutaneous injection of cabron tetrachloride was used to observe anti-fibrosis effect of CSBTA and to search its possible mechanisms.Colorimetry was used to measure the contents of ALT , AST , TP , ALB , MDA , SOD and Hyp.Radioimmunoassay( RIA ) was used to determine the contents of serum HA and LN.Light microscopic examination was used to watch morphological changes of hepatic tissue of acute liver injury and chronic hepatic fibrosis.The content of hepatic tissue TGF-β1 and MMP-9 were detected by immunohistochemical technique.
RESULTS:CSBTA could obviously decrease ALT and AST of animal model of acute liver injury induced by carbon tetrachloride and rat model of chronic hepatic fibrosis induced by subcutaneous injection of cabron tetrachloride(P<0.01, P<0.05),significantly decrease MDA level of liver tissue(P<0.01, P<0.05),increase activity of SOD of liver tissue (P<0.01, P<0.05),markedly increase levels of serum TP and ALB of hepatic fibrotic rats(P<0.01, P<0.05) and decrease Hyp level of liver tissue of hepatic fibrotic rats(P<0.01, P<0.05).The levels of HA and LN were also obviously decreased(P<0.01, P<0.05) in the rat model of chronic hepatic fibrosis.CSBTA could down-regulate the expression of TGF-β1 and MMP-9 of rat hepatic tissue(P<0.01, P<0.05).Under light microscopy,the CSBTA therapy groups could both significantly decrease the infiltration of inflammatory cells,hepatic cell degeneration,and necrosis in acute liver injury model,but also inhibit the generation of hepatic pseudolobuli and the sedimentation of collagenous fibers as compared with model group(P<0.01, P<0.05).
CONCLUSION:CSBTA has obviously protective effects on acute liver injury induced by carbon tetrachloride,and can block the formation of rat hepatic fibrosis produced by carbon tetrachloride. Its possible mechanisms may be related to the effect of anti-oxidation,inhibiton of collagen protein synthesis and promotion of extracellular matrix(ECM) degradation.
方法:通过复制四氯化碳(Carbon tetrachloride,CCl4)所致的小鼠急性肝损伤模型观察CSBTA的保肝作用;通过皮下注射四氯化碳,复制大鼠慢性肝纤维化模型,观察CSBTA的抗肝纤维化作用及其可能的作用机制。采用比色法测定ALT、AST、TP、ALB、MDA、SOD、Hyp含量,放射免疫法测定HA、LN含量,小鼠急性肝损伤和大鼠慢性肝纤维化肝组织进行HE染色并在光镜下观察其形态学变化,免疫组织化学染色观察慢性肝纤维化大鼠肝组织TGF-β1和MMP-9的表达情况。
结果: CSBTA可显著地降低大、小鼠血清中的ALT、AST含量(P<0.01, P<0.05),并能显著降低两者肝组织中MDA的水平(P<0.01, P<0.05)升高肝组织中SOD的活性(P<0.01, P<0.05);CSBTA也能降低大鼠肝组织中Hyp的含量(P<0.01, P<0.05)和大鼠血清TP、ALB含量(P<0.01, P<0.05),大鼠血清肝纤维化指标HA、LN也较模型组有明显下降(P<0.01, P<0.05);光镜下CSBTA给药组与模型组比较,可明显减少急性肝损伤时肝组织中的炎症细胞浸润、肝细胞变性和坏死,也可抑制慢性肝纤维化时肝假小叶的形成和胶原纤维沉积(P<0.01, P<0.05);免疫组化显示CSBTA可明显降低由CCl4引起的TGF-β1和MMP-9的升高, CSBTA给药组与模型组比较,两者的表达量明显降低(P<0.01, P<0.05)。
结论:岩黄连总碱对四氯化碳所致急性肝损伤具有明显保护作用,也可抑制大鼠慢性肝纤维化的形成。其机制可能与抗脂质过氧化、抑制胶原蛋白合成,促进细胞外基质降解有关。
OBJECTIVE: To investigate protective effects of Corydalis saxicola Bunting Total Alkaloids(CSBTA) on liver ,and to explore its possible mechanisms of protecting liver and anti-hepatic fibrosis.
METHODS: Animal model of acute liver injury induced by cabron tetrachloride was used to observe the protective effect of CSBTA on liver,model of chronic hepatic fibrosis established by subcutaneous injection of cabron tetrachloride was used to observe anti-fibrosis effect of CSBTA and to search its possible mechanisms.Colorimetry was used to measure the contents of ALT , AST , TP , ALB , MDA , SOD and Hyp.Radioimmunoassay( RIA ) was used to determine the contents of serum HA and LN.Light microscopic examination was used to watch morphological changes of hepatic tissue of acute liver injury and chronic hepatic fibrosis.The content of hepatic tissue TGF-β1 and MMP-9 were detected by immunohistochemical technique.
RESULTS:CSBTA could obviously decrease ALT and AST of animal model of acute liver injury induced by carbon tetrachloride and rat model of chronic hepatic fibrosis induced by subcutaneous injection of cabron tetrachloride(P<0.01, P<0.05),significantly decrease MDA level of liver tissue(P<0.01, P<0.05),increase activity of SOD of liver tissue (P<0.01, P<0.05),markedly increase levels of serum TP and ALB of hepatic fibrotic rats(P<0.01, P<0.05) and decrease Hyp level of liver tissue of hepatic fibrotic rats(P<0.01, P<0.05).The levels of HA and LN were also obviously decreased(P<0.01, P<0.05) in the rat model of chronic hepatic fibrosis.CSBTA could down-regulate the expression of TGF-β1 and MMP-9 of rat hepatic tissue(P<0.01, P<0.05).Under light microscopy,the CSBTA therapy groups could both significantly decrease the infiltration of inflammatory cells,hepatic cell degeneration,and necrosis in acute liver injury model,but also inhibit the generation of hepatic pseudolobuli and the sedimentation of collagenous fibers as compared with model group(P<0.01, P<0.05).
CONCLUSION:CSBTA has obviously protective effects on acute liver injury induced by carbon tetrachloride,and can block the formation of rat hepatic fibrosis produced by carbon tetrachloride. Its possible mechanisms may be related to the effect of anti-oxidation,inhibiton of collagen protein synthesis and promotion of extracellular matrix(ECM) degradation.
引文
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