重组牛胰蛋白酶抑制剂对四氯化碳致大鼠慢性肝损伤的保护作用

目的观察重组牛胰蛋白酶抑制剂(rBPTI)对大鼠慢性肝损伤的保护作用。方法大鼠98只,随机分成7组,分别为正常对照组、模型组、rBPTI3个剂量组(20,40和80MU.kg-1)、抑肽酶组(80MU.kg-1)和促肝细胞生长素组(100mg.kg-1)。除正常对照组外,其余各组皮下注射四氯化碳制备慢性肝损伤模型。8周后每天ip给药,给药4周后测定血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性、白蛋白(Alb)含量、白蛋白/球蛋白(A/G)比值、唾液酸(SA)含量及肝组织羟脯氨酸(Hyp)含量,并进行组织病理学检测。结果与正常对照组比较,模型组大鼠血清GPT和GOT活性、SA含量及肝组织Hyp含量明显升高,血清Alb含量和A/G比值明显降低。与模型组比较,rBPTI各剂量组大鼠血清GPT和GOT活性、SA含量及肝组织Hyp含量降低,血清Alb含量和A/G比值明显增高。肝组织病理观察显示,rBPTI明显减轻由四氯化碳所致肝细胞脂肪变性及纤维组织增生等病理改变。结论rBPTI对四氯化碳诱导的大鼠慢性肝损伤具有保护作用和抗纤维化作用,在所观察的剂量范围内作用效果与抑肽酶相当。

Protective effect of recombinant bovine pancreatic trypsin inhibitor on chronic liver injury induced by carbon tetrachloride in rats

AIM To observe the protection of recombinant bovine pancreatic trypsin inhibitor (rBPTI) against chronic liver injury. METHODS Ninety eight rats were randomized into 7 groups: normal control, model control, rBPTI 20, 40 and 80 MU·kg^-1, aprotinin 80 MU·kg^-1 and hepatocyte growth-promoting factor (pHGF) 100 mg·kg^-1 groups. The chronic liver injury rat model was induced by carbon tetrachloride (CCl₄). After 8 weeks, the rats were administered (ip) with rBPTI, aprotinin or pHGF daily for 4 weeks except that in normal and model control groups. The glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) activities, albumin (Alb) content, Alb and globulin content ratio (A/G), sialic acid (SA) content in serum were measured. Hydroxyproline (Hyp) level and histopathological changes of hepatic tissue were also examined. RESULTS Compared with normal control group, the activities of serum GPT and GOT, and the contents of SA in serum and Hyp in liver tissue in model group were increased, and the content of serum Alb and A/G ratio were decreased．Compared with model group, rBPTI (20, 40 and 80 MU·kg^-1) decreased the activities of GPT and GOT, and the contents of SA in serum and Hyp in liver tissue. The content of serum Alb and A/G ratio were increased by rBPTI. In addition, rBPTI alleviated chronic hepatic injuries such as fatty degeneration and liver fibrosis significantly. CONCLUSION rBPTI has protective and anti-fibrosis effects against chronic liver injury induced by CCl₄, and the efficiency is equivalent as aprotinin in the observed dosages.