Wang L, Lu W, Gao Y H, Cao X, Pei F, Liu X E, Zhuang H
Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Zhonghua Gan Zang Bing Za Zhi. 2019 Apr 20;27(4):267-273. doi: 10.3760/cma.j.issn.1007-3418.2019.04.006.
To investigate the effect of anluohuaxianwan (ALHXW) using rat model of carbon tetrachloride (CCl(4)) induced liver fibrosis on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Thirty-six male Wistar rats were randomly assigned into control, model and treatment groups. Rats in the model and treatment groups were injected intraperitoneally with 40% CCl(4) (2 ml/kg), and the control group were given isotonic saline twice a week for six weeks. Meanwhile, the treatment group were gavaged with ALHXW solution daily (concentration 0.15 g/ml, 9.9 ml/kg) for 6 weeks, while the control and model groups were given isotonic saline once a day for 6 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the end of third and sixth week. At the end of six weeks, liver tissues were harvested for histopathological evaluation and the detection of mRNA and protein expression levels of MMP-2/13 and TIMP-1/2. According to different data, LSD method, parametric (one-way ANOVA) and non-parametric tests (Kruskal-Wallis H-test and Mann-Whitney U test) were used for statistical analysis. Compared with the model group, ALHXW markedly alleviated liver injury in the treatment group, and thereby improved the general state of rats, liver and spleen morphological characteristics, and ALT and AST levels. Histopathological examination demonstrated that the extent of liver fibrosis was improved (2.75 ± 0.75 vs. 3.55 ± 0.69, = 0.015) in the treatment group as compared with the model group. The mRNA and protein expression levels of MMP-13 in the treatment group were significantly higher than that of the model group (mRNA: 10.50 ± 7.64 vs. 4.40 ± 2.97, = 0.029. Protein: 1.15 ± 0.09 vs. 0.78 ± 0.21, = 0.016), whereas the mRNA and protein expression levels of MMP-2, TIMP-1/2 in the treatment group were significantly lower than that of the model group (mRNA: 4.55 ± 3.29 vs. 7.83 ± 4.19, = 0.048; 1.66 ± 0.73 vs. 3.69 ± 2.78, = 0.023; 2.25 ± 1.16 vs. 3.41 ± 1.51, = 0.049; respectively. Protein: 0.44 ± 0.11 vs. 0.65 ± 0.05, = 0.03; 0.69 ± 0.06 vs. 1.07 ± 0.21, = 0.016; 0.46 ± 0.09 vs. 0.81 ± 0.13, = 0.003; respectively). ALHXW exerts anti-liver fibrosis effects mainly by improving liver function, inhibiting the activation of hepatic stellate cells, enhancing the expression of MMP-13, and inhibiting the expression of MMP-2 and TIMP-1/2.
采用四氯化碳（CCl₄）诱导的大鼠肝纤维化模型，研究安络化纤丸（ALHXW）对基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）表达的影响。将36只雄性Wistar大鼠随机分为对照组、模型组和治疗组。模型组和治疗组大鼠腹腔注射40% CCl₄（2 ml/kg），对照组每周两次给予等渗盐水，共6周。同时，治疗组每日灌胃给予ALHXW溶液（浓度0.15 g/ml，9.9 ml/kg），持续6周，而对照组和模型组每日给予等渗盐水，持续6周。在第3周和第6周结束时测量血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平。在6周结束时，采集肝组织进行组织病理学评估，并检测MMP - 2/13和TIMP - 1/2的mRNA和蛋白表达水平。根据不同数据，采用LSD法、参数检验（单因素方差分析）和非参数检验（Kruskal - Wallis H检验和Mann - Whitney U检验）进行统计分析。与模型组相比，ALHXW显著减轻了治疗组的肝损伤，从而改善了大鼠的一般状态、肝脏和脾脏形态特征以及ALT和AST水平。组织病理学检查表明，与模型组相比，治疗组肝纤维化程度有所改善（2.75±0.75 vs. 3.55±0.69，P = 0.015）。治疗组MMP - 13的mRNA和蛋白表达水平显著高于模型组（mRNA：10.50±7.64 vs. 4.40±2.97，P = 0.029；蛋白：1.15±0.09 vs. 0.78±0.21，P = 0.016），而治疗组MMP - 2、TIMP - 1/2的mRNA和蛋白表达水平显著低于模型组（mRNA：4.55±3.29 vs. 7.83±4.19，P = 0.048；1.66±0.73 vs. 3.69±2.78，P = 0.023；2.25±1.16 vs. 3.41±1.51，P = 0.049；蛋白：0.44±0.11 vs. 0.65±0.05，P = 0.03；0.69±0.06 vs. 1.07±0.21，P = 0.016；0.46±0.09 vs. 0.81±0.13，P = 0.003）。ALHXW主要通过改善肝功能、抑制肝星状细胞活化、增强MMP - 13表达以及抑制MMP - 2和TIMP - 1/2表达发挥抗肝纤维化作用。
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