胡黄连苷Ⅱ对大鼠胆管结扎胆汁淤积的改善作用

Effects of picroside Ⅱ on cholestatic liver injury in rats induced by bile duct ligation

目的考察胡黄连苷II(PSII)对大鼠胆管结扎胆汁淤积模型的改善作用。方法采用胆总管结扎建立大鼠胆汁淤积模型,另取10只大鼠只分离胆管不结扎,作为假手术组(0.5%CMC-Na),50只胆管结扎大鼠随机分为5组:模型组(0.5%CMC-Na)、熊去氧胆酸(UCDA)100 mg/kg阳性药组和PSII 80、40和20 mg/kg组,造模后各组连续ig给药7 d。观察大鼠一般状况及体质量;试剂盒法检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBIL)、总胆汁酸(TBA)水平;取肝脏称质量,计算肝脏系数;试剂盒法测定肝脏组织匀浆中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性,匀浆上清液中髓过氧化物酶(MPO)活性。结果与模型组比较,PSII对模型大鼠一般状态和体质量无明显影响,可显著降低模型大鼠肝脏系数(P<0.01、0.05);PSII 80、40 mg/kg给药均可显著降低模型大鼠血清ALT、AST、ALP、GGT、TBIL水平,80 mg/kg对血清TBA也发挥显著降低作用(P<0.01);PSII 80、40 mg/kg给药均可显著升高肝脏SOD和CAT活性(P<0.05、0.01),对肝脏GSH-Px活性未见明显影响,均可显著降低肝脏MPO活性(P<0.05、0.01)。结论 PSII对于大鼠胆管结扎所致的胆汁淤积性肝损伤具有明显的改善作用,涉及的机制可能包括上调肝组织抗氧化酶活性及抑制炎性细胞活化和浸润。

Objective To investigate the effect of picroside Ⅱ (PSⅡ) on the cholestasis of bile duct ligation in rats. Methods Cholestasis model was established by common bile duct ligation, another 10 rats were separated from the bile duct without any ligature as the sham operation group (0.5% CMC-Na). Fifty rats with bile duct ligation were randomly divided into five groups:model group (0.5% CMC-Na), UCDA (100 mg/kg, positive drug) group, PSⅡ 80, 40 and 20 mg/kg group. After modeling, rats in each group were ig administered continuously for 7 days. The general condition and body weight of rats were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL) and total bile acid (TBA) were measured by kit method. The liver weight was taken to calculate the liver coefficient, and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in liver homogenate and myeloperoxidase (MPO) in the supernatant of liver homogenate were determined by kit method. Results Compared with the model group, PSⅡ had no significant effect on the general state and body weight of the model rats, but could significantly reduce the liver coefficient of the model rats (P<0.01, 0.05); The serum levels of ALT, AST, ALP, GGT, and TBIL in model rats were significantly decreased after 80 and 40 mg/kg PSⅡ administration, and serum TBA was also significantly reduced by 80 mg/kg (P<0.01). PSII 80 and 40 mg/kg administration could significantly increase the activity of SOD and CAT in liver, but there was no significant difference in liver GSH-Px activity,and both 80 and 40 mg/kg PSII administration significantly reduced liver MPO activity (P<0.01, 0.05).Conclusion PSII can significantly improve cholestatic liver injury caused by bile duct ligation in rats.The mechanisms involved may include up-regulating the activity of antioxidant enzymes in liver and inhibiting activation and infiltration of inflammatory cells.