AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction (HYRD) on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) β-Smad signaling pathway.METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n = 6), CCl4-induced hepatic fibrosis group (n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n = 12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl4 dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff I (80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff II (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III precollagen (PCIII) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively.RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P < 0.01), and they were decreased in the three treatment groups compared with the model group. The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups. The hepatic hydroxyproline content and serum levels of PCIII, HA, LN and CIV were markedly increased in the model group compared with the control group, and decreased in the treatment groups. The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group, and HYRD could down regulate their expression.CONCLUSION: HYRD can inhibit hepatic fibrosis induced by CCl4 in rats, which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.
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机译：目的：探讨蒿胆养阴软煎汤对CCl4诱导的大鼠肝纤维化的抗纤维化作用及其对转化生长因子（TGF）β-Smad信号通路的调节作用。方法：五十六只健康的Wistar大鼠随机分为五组：正常对照组（n = 6），CCl4诱导的肝纤维化组（n = 14）和三个治疗组（治疗的大鼠通过口服口服HYRD，每日剂量分别为8.2、2.5和0.82 g / kg）的HYRD（分别为n = 12）。首次皮下注射0.5 mL / 100 g体重的四氯化碳溶液（CCl4溶于花生油，4：6，V / V）诱导实验性肝纤维化，然后两次皮下注射0.3 mL / 100 g体重每周8周。在前两周，饲料I（80％玉米粉，20％猪油，0.5％胆固醇）喂养大鼠。 2周后，用饲料II（玉米粉和0.5％胆固醇）饲养它们。除对照组外，从头开始每隔一天给每只大鼠口服30％的酒精溶液，每只大鼠1毫升。通过色谱法检测肝功能参数和肝羟脯氨酸含量。用放射免疫测定法测定血清透明质酸（HA），IV型胶原蛋白（CIV），III型前胶原（PCIII）和层粘连蛋白（LN）的水平。用苏木精-伊红染色和胶原染色观察到胶原的沉积。实时逆转录-聚合酶链反应和Western blotting检测TGFβ1和Smad3的基因表达。结果：模型组血清丙氨酸转氨酶和天冬氨酸转氨酶水平较对照组升高（P <0.01）。 ），并且在三个治疗组中与模型组相比有所降低。模型组的血清总蛋白和白蛋白水平降低，而三个治疗组的血清水平升高。与对照组相比，模型组肝脏羟脯氨酸含量和PCIII，HA，LN和CIV血清水平明显升高，而治疗组则降低。与对照组相比，模型组TGFβ1和Smad3的基因表达增强，HYRD可能下调其表达水平。结论：HYRD可以抑制CCl4诱导的大鼠肝纤维化，可能与其下调CCl4表达有关。 TGFβ-Smad途径的纤维化信号转导。
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