岩藻黄质调控TGF-β/Smad3信号通路减轻CCl4诱导的大鼠肝纤维化和氧化应激

目的： 探究岩藻黄质对肝纤维化模型大鼠氧化应激和纤维化的保护作用及可能机制。方法： 将雄性SD大鼠随机分为空白、模型、岩藻黄质和水飞蓟宾组。除空白组外，其余各组大鼠均皮下注射CCl₄溶液，2次/周，连续8周。造模同时，各组给予相应药物，空白和模型2组均给予等体积无菌水。8周后处死大鼠，检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（T-BIL）、直接胆红素（D-BIL）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽-过氧化物酶（GSH-Px）、透明质酸（HA）、羟脯氨酸（HYP）、层粘连蛋白（LN）含量以及α-SMA、TGF-β/Smad3通路主要mRNA和蛋白表达；并检测肝组织病理变化和纤维化。结果： 与空白组比较，模型组大鼠血清AST、ALT、T-BIL、D-BIL、HA、HYP、LN、MDA，肝组织α-SMA mRNA和α-SMA、TGF-β、p-Smad3蛋白水平显著上调，而SOD和GSH-Px含量降低，肝脏可见细胞结构破坏，大量炎症细胞浸润，胶原沉积和纤维增生；与模型组相比，岩藻黄质和水飞蓟宾可显著逆转大鼠血清ALT、AST、T-BIL、D-BIL、HA、HYP、LN和MDA的升高及SOD和GSH-Px的降低，并缓解肝组织炎症和纤维化程度；此外，岩藻黄质可显著抑制肝组织α-SMA、TGF-β mRNA和α-SMA、TGF-β、p-Smad3蛋白表达水平。结论： 岩藻黄质通过抑制TGF-β/p-Smad3通路缓解大鼠肝纤维化水平，调节氧化应激状态。

Fucxanthine inhibits hepatic fibrosis and oxidative stress induced by CCl4 in rats via regulating TGF-β/Smad3 signaling pathway

OBJECTIVE To explore the protective effect and possible mechanism of fucxanthine on oxidative stress and fibrosis in rats model with hepatic fibrosis.METHODS Male rats were randomly divided into normal, model, Fucxanthine and Silybin groups.Except for the normal group, the rats in other groups were treated with subcutaneous CCl₄ solution twice a week for 8 consecutive weeks.At the same time, the rats in the Fucxanthine group and the Silybin group were given corresponding drugs, and the other two groups were given sterile water of the same volume.The rats were sacrificed eight weeks later, serum aspertate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin(T-BIL), direct bilirubin(D-BIL), superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), hyaluronic acid(HA), hydroxyproline(HYP), layer adhesion protein(LN) content and the mRNA and protein of α-SMA, TGF-β and Smad3 in liver tissue were detected;HE staining and Masson staining were used to observe the pathological damage and fibrosis of liver tissue.RESULTS Compared with normal group, model group rats serum AST, ALT, T-BIL, D-BIL, HA, HYP, LN, MDA content and α-SMA mRNA, α-SMA, TGF-β, p-Smad3 protein levels increased, while SOD and GSH-Px contents decreased significantly.Compared with the model group, Fucxanthine and Silybin could significantly reverse the elevation of serum ALT, AST, T-BIL, D-BIL, HA, HYP and LN caused by CCl₄, restore liver function, relieve inflammation and fibrosis in liver tissues of rats, and significantly reduce MDA and increase SOD and GSH-Px contents.In addition, Fucxanthine and Silybin significantly inhibited the expression levels of α-SMA, TGF-β mRNA and α-SMA, TGF-β, p-Smad3 protein in liver tissue.CONCLUSION Fucxanthine can alleviate rat hepatic fibrosis and regulate oxidative stress by inhibiting TGF-β/p-Smad3 pathway.