四氯化碳、硫代乙酰胺和猪血清诱导大鼠肝纤维化模型的比较

目的：比较采用四氯化碳（CCl4），硫代乙酰胺（TAA）及猪血清诱导3种方式制备大鼠肝纤维化模型的效果和特点。方法：将72只SD大鼠随机均分为：CCl4组，TAA组，猪血清组及对照组，分别每周2次皮下注射40% CCl4（0.5 mL/100 g），0.03% TAA（200 mg/kg），猪血清（0.5 mL/只）和生理盐水（0.1 mL/kg）。观察大鼠一般情况及体重变化；在造模第3，6，9周末，测定大鼠血清中的天冬氨酸氨基转移酶（AST），谷氨酸氨基转移酶（ALT），丙二醛（MDA），透明质酸（HA）水平；取肝组织进行HE染色，观察肝组织结构变化，并对肝纤维化程度进行分级和评分。结果：CCl4，TAA组大鼠体重增加量均明显低于对照组（均P<0.05），而猪血清组与对照组间体重增加量差异无统计学意义（P>0.05）；TAA组3个时间点ALT浓度均明显升高（均P<0.05），而CCl4组和猪血清组ALT无明显升高。CCl4组AST浓度在第3周明显升高（P<0.05），但在第6，9周有所下降，TAA组3个时间点AST浓度均明显升高（均P<0.05），猪血清组AST浓度无明显升高。3个实验组MDA和HA浓度在3个时点间均有所升高（均P<0.05），两者均在TAA组升高最明显；3个实验组第9周均可见不同程度的肝细胞颗粒样变，汇管区纤维组织异常增生；与对照组比较，3个实验组的肝纤维化分级和SSS计分差异均具有统计学意义（均P<0.05），第9周时，TAA组的SSS计分高于CCl4组（P<0.05），而CCl4组的SSS评分高于猪血清组（P<0.05）。结论：3种方法均可诱导大鼠肝纤维化模型，TAA效果略优于CCl4。猪血清法造模对动物整体损伤较轻微。

Comparison of rat models of hepatic fibrosis induced by carbon tetrachloride, thioacetamide and porcine serum

Objective: To investigate the effects and features of three methods, namely, carbon tetrachloride (CCl4), thioacetamide (TAA) and porcine serum induction, to create hepatic fibrosis in rats. Methods: Seventy-two SD rats were equally randomized into CCl4 group, TAA group, porcine serum group and control group, and then the rats were subcutaneously injected with 40% CCl4 (0.5 mL/100 g), 0.03% TAA (200 mg/kg), porcine serum (0.5 mL/per rat) and normal saline (0.1 mL/kg) twice a week, respectively. The general status and body weight changes of the rats were observed. At the end of the 3rd, 6th and 9th week of the experiment, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA) and malondialdehyde (MDA) of the rats were detected, and HE staining was performed on the rat liver tissues to observe the morphological changes of the liver tissues, and to stage and score the degree of liver fibrosis, respectively. Results: The body weight gain of rats in CCl4 group and TAA group was significantly lower than that in control group (both P<0.05), but it had no significant difference between the porcine serum group and control group. The ALT levels at the three time points of TAA group were all significantly increased (all P<0.05), while there was no obvious elevation in CCl4 group and porcine serum group. The AST level increased significantly at the 3rd week but declined to some extent at the 6th and 9th week, and it increased significantly in TAA group at each time point (all P<0.05) and had no obvious change in porcine serum group. The MDA and HA levels of the three experimental groups all increased to some extent at the three time points (all P<0.05), and both MDA and HA levels increased most obviously in TAA group. At the 9th week, all the three experimental groups exhibited varying degrees of granular degeneration of the hepatic cells and abnormal proliferation of fibrous tissue in the portal tracts. The stages and SSS scores of liver fibrosis of the three experimental groups were all significantly different from those of the control group (all P<0.05). At the 9th week, the SSS score of the TAA group was higher than that of the CCl4 group (P<0.05), while CCl4 group was higher than porcine serum group (P<0.05). Conclusion: All the three methods can induce hepatic fibrosis in rats, and the effect of TAA is slightly better than CCl4. The method of porcine serum induction exerts minor overall injury to the animals.