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目的研究促肝细胞生长素(PHGF)对α-萘异硫氰酸酯(ANIT)致小鼠急性肝损伤的保护作用及机制,为其临床应用提供实验依据。方法 50只BALB/c雄性小鼠,随机分为对照组10只和ANIT处理组40只。ANIT处理组小鼠口服105 mg/kg ANIT后随机分为模型组、重组人肝细胞生长因子组(ANIT+rh HGF 1μg)、促肝细胞生长素低剂量组(ANIT+PHGF 10 mg/kg)、促肝细胞生长素高剂量组(ANIT+PHGF 20 mg/kg)。对照组和模型组小鼠在口服ANIT前0.5 h,口服ANIT后6,12,24,30,36 h腹腔注射生理盐水;ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组和ANIT+PHGF 20 mg/kg组小鼠分别在相同时间点腹腔注射1μg rh HGF、10 mg/kg PHGF和20 mg/kg PHGF;口服ANIT后48 h,麻醉小鼠并心脏取血,血液离心后,取血清,检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)的含量。取肝脏,部分肝脏用10%甲醛溶液固定,切片后进行HE染色,观察其病理变化;部分肝脏液氮保存,检测超氧化物歧化酶(SOD)的活性。结果 ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组和ANIT+PHGF 20 mg/kg组小鼠ALT、AST、ALP含量比模型组显著降低。模型组与对照组SOD含量比较,显著增加;ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组、ANIT+PHGF 20 mg/kg组与模型组SOD含量相比较,无明显差异。HE染色结果显示,ANIT+rh HGF 1μg、ANIT+PHGF 10 mg/kg和ANIT+PHGF 20 mg/kg组小鼠肝脏坏死和炎性细胞浸润情况明显减轻。结论 PHGF能保护ANIT急性小鼠肝损伤,其作用机制可能与抑制炎症反应有关。
Objective To investigate the protective effect of hepatocyte growth-promoting factor (PHGF) on acute hepatic injury induced by α-naphthalene isothiocyanate (ANIT) in mice and provide experimental evidence for its clinical application. Methods Fifty BALB / c male mice were randomly divided into control group (n = 10) and ANIT group (n = 40). The ANIT-treated mice were orally administered with 105 mg / kg of ANIT and were randomly divided into model group, recombinant human hepatocyte growth factor (ANIT + rh HGF 1 μg), low dose of hepatocyte growth factor (ANIT + PHGF 10 mg / kg) , High-dose of hepatocyte growth factor (ANIT + PHGF 20 mg / kg). Control group and model group mice were intraperitoneally injected with normal saline 0.5 h before oral administration of ANIT, 6,12,24,30,36 h after oral administration of ANIT, ANIT + rh HGF 1μg group, ANIT + PHGF 10 mg / kg group and ANIT + The mice in PHGF 20 mg / kg group were intraperitoneally injected with 1 μg rhGFP, 10 mg / kg PHGF and 20 mg / kg PHGF respectively at the same time point. After 48 hours of oral administration of ANIT, the mice were anesthetized and the heart was centrifuged Serum levels of ALT, AST and ALP were measured. The liver was taken, and part of the liver was fixed with 10% formalin. The sections were stained with hematoxylin-eosin (HE) to observe the pathological changes. Some liver samples were stored in liquid nitrogen to detect the activity of superoxide dismutase (SOD). Results The levels of ALT, AST and ALP in ANIT + rh HGF 1 μg group, ANIT + PHGF 10 mg / kg group and ANIT + PHGF 20 mg / kg group were significantly lower than those in model group. There was no significant difference in the content of SOD between the model group and the control group in the ANIT + rh HGF 1μg group, the ANIT + PHGF 10 mg / kg group and the ANIT + PHGF 20 mg / kg group. The results of HE staining showed that the liver necrosis and inflammatory cell infiltration in the mice treated with ANIT + rh HGF 1μg, ANIT + PHGF 10 mg / kg and ANIT + PHGF 20 mg / kg were significantly reduced. Conclusions PHGF can protect liver injury of ANIT acute mice, which may be related to the inhibition of inflammatory reaction.