玉郎伞多糖对双氯芬酸致小鼠肝损伤的保护作用及相关机制研究

Protective effect of Yulangsan polysaccharide on hepatic injury induced by diclofenac in mice and its relative mechanism

目的:探讨玉郎伞多糖(Yulangsan polysaccharide,YLSPS)对双氯芬酸(Diclofenac,DICF)致小鼠肝损伤的保护作用及相关机制研究。方法:把昆明种小鼠随机分为正常对照组(normal control,NC),DICF损伤模型组,YLSPS高(YLSPSH,600 mg/kg)、YLSPS中(YLSPSM,300 mg/kg)、YLSPS低(YLSPSL,150 mg/kg)剂量组和联苯双酯阳性对照组(dimethyl diphenyl bicarboxylate,200 mg/kg DDB),每组10只。YLSPS高、中、低剂量组和联苯双酯组灌胃给予相应药物,正常对照组和模型组同法给予相等容积的生理盐水,每日1次,连续14 d。末次给药后1 h,除正常组给予相等容量生理盐水腹腔注射外,其余各组小鼠同法给予DICF 50 mg/kg。造模后动物禁食20 h,取血及脏器检测肝功能指标碱性磷酸酶(alkaline phosphatase,ALP)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及总胆红素(total bilirubin,TBIL),检测肝匀浆超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、丙二醛(malondialdehyde,MDA)和过氧化氢酶(catalase,CAT)的水平及血清中白介素-1β(interleukin-1β,IL-1β)水平,HE(Hematoxylin eosin)染色法观察各组小鼠肝细胞损伤程度。结果:与模型对照组比较,YLSPS能降低血清ALT、AST、ALP活性和TBIL含量以及肝组织MDA含量(P<0.05),能降低血清TNF-α、IL-1β水平(P<0.05),提高肝组织SOD、GSH-Px以及CAT活性(P<0.05)。结论:YLSPS能够有效减轻肝细胞损伤程度,对DICF所致的小鼠肝损伤具有保护作用,机制可能与抗氧自由基及抑制脂质过氧化等作用有关。

Objective：To observe the protective effect of Yulangsan polysaecharide（YLSPS）on diclofenac-induced liver injury in Kunming mice. Methods：The models of diclofenac-induced liver injury in mice with method of injection were used to study the pro-tective effect of YLSPS. Kunming mice were randomly divided into liver injured DICF group,NC group,YLSPS high-,middle-,lowgroup（600,300,150 mg/kg）and dimethyl diphenyl bicarboxylate（200 mg/kg DDB）group. The treatment groups were orally administered once per day whereas the normal and model groups were orally administered with saline for 14 d. Except normal group,all the other mice were injected intraperitoneally with DICF（50 mg/kg body weight）. After fasting for 20 h,animals were sacrificed and blood,liver samples were obtained. The levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphatase（ALP）,total bilirubin（TBIL）,tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）in serum and levels of superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）,catalase（CAT）,malondialdehyde（MDA） in liver tissue were measured. Hematoxylineosin（HE）stain was used to examine the degree of hepatic injury. Results：Compared with model group,YLSPS could reduce the levels of ALT,AST,ALP,TBIL,MDA,TNF-α and IL-1β.The activities of GSH-Px,SOD,and CAT could be increased（P〈0.05）,and the degree of hepatic injury could be lessened.Conclusion：YLSPS has protective effect on diclofenac-induced liver injury in mice. The mechanism may be related to attenuating free radical and inhibiting the effect on lipid peroxidation.