束缚应激对D-氨基半乳糖联合脂多糖诱导小鼠肝损伤的保护作用

目的探讨束缚应激对D-氨基半乳糖联合脂多糖（D–galactosamine and lipopolysaccharide combination,D＋L）诱导的小鼠肝损伤的保护作用。方法正常BALB/c小鼠随机分为正常对照组（con）、应激对照组（str）、模型组（D＋L）、束缚应激组（D＋L＋str）。con组小鼠常规饲养;str组小鼠给予定时定量的束缚应激;D＋L组小鼠腹腔注射D-氨基半乳糖和脂多糖的混合溶液,1次/2天;D＋L＋str组小鼠腹腔注射等量D＋L混合液后,给予与str组相同的束缚应激。第8周,各组小鼠取血检测血清AST、ALT,肝脏固定后HE及Masson染色观察小鼠肝脏结构、细胞形态及纤维化程度。结果第8周D＋L＋str组与D＋L组小鼠相比,血清ALT和AST显著降低（P〈0.01）,AST/ALT显著增高（P〈0.01）;HE及Masson染色显示,D＋L组小鼠肝小叶结构紊乱,出现结节性增生及大量上皮细胞核浓缩、溶解、坏死,枯否氏细胞浸润,而D＋L＋str组未见明显病理变化;纤维化程度评分显示,D＋L＋str组与D＋L组小鼠相比,病理评分与纤维显色吸光度值均显著降低（P〈0.05）。结论束缚应激对D＋L诱导的小鼠肝损伤具有一定保护作用。

Protective effect of restraint stress on mouse liver injury induced by D-galactosamine and lipopolysaccharide

Objective To investigate the effect of restraint stress on liver injury in mice induced by D-galactosamine and lipopolysaccharide （D＋L）.Methods Normal BALB/c （B/c） mice were randomly divided into normal control, stress control, D＋L group, and D＋L＋stress group.The mice of normal control group were bred routinely.The stress group was given stress regularly and quantitatively.Mice in the D＋L group were injected intraperitoneally with mixed solution of D-galac-tosamine and lipopolysaccharide at final concentration of 30 mg/mL and 2μg/mL, respectively, once every two days.The D＋L＋stress group was given equal stress as stress group after injection of D-galactosamine and lipopolysaccharide mixed solution. Eight weeks later, blood samples were collected to test serum aminotransferase （ALT） and aspartate aminotransferase （AST）, liver tissue samples from all animals were collected to evaluate the degree of liver fibrosis by HE and Masson staining.Results At the 8th week, the ALT and AST values in the D＋L＋stress group were significantly reduced（ P〈0.01） and AST/ALT value was significantly increased（P〈0.01）compared with that in the D＋L group.For HE and Masson staining, disordered structure of hepatic lobules, nodular hyperplasia, and necrosis of epithelial cells were present in animals of the D＋L group.However, no obvious pathological changes were observewd in the D＋L＋stress group.For fibrosis scores, the fibrosis grade in the D＋L＋stress group was significantly decreased than that of the D＋L group （P〈0.05）.Conclusions Constraint stress presents pro-tective effect on D-galactosamine and lipopolysaccharide induced liver injury in mice.