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目的:比较狗肝菜不同分子量多糖对四氯化碳所致大鼠急性肝损伤的保肝降酶作用,研究其可能的保肝机制。方法:将70只雄性SD大鼠随机分成模型、联苯双酯、狗肝菜总多糖(A组)、相对分子质量<6 000狗肝菜多糖(B组)、相对分子质量6 000~10 000狗肝菜多糖(C组)和相对分子质量>10 000狗肝菜多糖(D组)和对照组;A组(250 mg.kg-1)、B组(500 mg.kg-1)、C组(150 mg.kg-1)和D组(300 mg.kg-1)、联苯双酯组(150 mg.kg-1)在造模前灌胃给药7 d,其他各组用生理盐水对照;在末次给药1 h除对照组外,均灌胃0.1%CCl4花生油(0.01 mL.g-1)建立大鼠急性肝损伤模型,对照组用生理盐水对照。于16 h行腹主动脉取血用于检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP);肝组织中超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量及肝脏病理形态学变化;计算肝脏指数(肝体比)、脾脏指数(脾体比)、肾脏指数(肾体比)。结果:与正常对照组比较,模型组大鼠血清中ALT,AST,TP水平显著升高(P<0.01),提示本实验模型成功。狗肝菜各多糖组大鼠血清ALT,AST活性降低与模型组比较有显著性差异(P<0.01),A,B组可显著减少由于肝损伤造成的TP升高,与模型对照组比较,差异具有统计学意义(P<0.05或P<0.01),其中B组效果最佳;与模型对照组比较,A,B组升高SOD活性(P<0.05或P<0.01);A,C组升高GSH-Px活性,(P<0.01);对于MDA含量狗肝菜多糖各部位组降低均具有统计学意义(P<0.01);模型肝组织大片坏死、淤血,狗肝菜多糖各给药组组织损伤程度明显降低,以B组效果最佳;对于肝脏指数,D组效果最优(P<0.05)。结论:狗肝菜各多糖组均对CCl4所致大鼠急性肝损伤效果显著,综合分析相对分子质量<6 000组(B组)保肝效果最佳。
OBJECTIVE: To compare the hepatoprotective effect of different molecular weight polysaccharides of DOG with different doses on hepatoprotective effect of CCl4-induced acute liver injury in rats and to study its possible mechanism of protecting liver. Methods: Seventy male Sprague Dawley rats were randomly divided into four groups: model, bifendate, total proteoglycan from group A, relative molecular weight less than 6 000, and group B with relative molecular mass of 6 000 to 10 000 Group C and 150 mg.kg-1 in group B, 500 mg.kg-1 in group B, 100 mg.kg- 1) and group D (300 mg.kg-1). The bifendate group (150 mg.kg-1) was given intragastrically for 7 days before modeling. The other groups were given saline. 1 h except the control group, rats were injected intraperitoneally with 0.1% CCl4 peanut oil (0.01 mL.g-1) to establish acute liver injury model in the control group with normal saline control. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total protein (TP) were measured at 16 h. The activity of superoxide dismutase (SOD) (GSH-Px) activity, malondialdehyde (MDA) content and pathological changes of liver were calculated. Liver index (liver ratio), spleen index (spleen ratio), kidney index ). Results: Compared with the normal control group, the levels of ALT, AST and TP in the model group were significantly increased (P <0.01), suggesting that the experimental model was successful. Compared with model group, the decrease of serum ALT and AST in each group of Hepaticus hepatica polysaccharide group was significantly different (P <0.01). Group A and B could significantly reduce the increase of TP caused by liver injury compared with model control group, the difference was (P <0.05 or P <0.01), and the effect was the best in group B; Compared with the model control group, the activity of SOD in group A and B increased (P <0.05 or P <0.01) GSH-Px activity (P <0.01). The content of MDA was significantly decreased in all groups (P <0.01). The damage of liver tissue in model group was significantly decreased , With the best effect in group B; for the liver index, group D was the best (P <0.05). Conclusion: The results showed that all the polysaccharides of Hepaticus hepatica had a significant effect on CCl4-induced acute liver injury in rats. The relative molecular mass of <6 000 groups (group B) had the best hepatoprotective effect.