大黄酸对大鼠肝纤维化形成的影响

目的观察大黄酸对肝纤维化形成的影响。方法采用体积分数60％的CCl4及5％的乙醇制备肝纤维化动物模型,分别用小剂量、大剂量大黄酸干预,测定血清丙氨酸氨基转移酶(ALT)、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)及肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,免疫组织化学方法观察抗转化生长因子β1(TGFβ1)、α平滑肌肌动蛋白(α-SMA)的表达情况,并观察肝组织胶原面积及病理变化。 结果(1)血清ALT(U/L)、HA(μg/L)、PCⅢ(μg/L)水平及肝组织中MDA(nmol/mg)含量,大黄酸大剂量组分别为78±18、217±75、16±6和1.88±0.34,模型对照组分别为150±16、321±97、31±14和3.67±0.68,两组比较t值分别为7.831、2.977、3.249和6.751,差异有非常显著性(P<0.01)。肝组织中SOD活性(NU/mg蛋白)大黄酸大剂量组为91.26±14.04,模型对照组为62.45±8.74(t=4.453,P<0.01)。(2)肝组织中TGFβ1、α-SMA的表达显著减少(P<0.05或P<0.01)。(3)肝组织胶原面积明显减少,纤维化程度明显改善(P<0.05或P<0.01)。结论大黄酸具有保肝作用和抗肝纤维化作用,其作用机制可能与其抗炎、抗氧化作用及抑制TGFβ1的活性、抑制肝星状细胞活化有关。

Effect of Rhein on the development of hepatic fibrosis in rats

Objective To investigate the effect of rhein on the development of hepatic fibrosis. Methods The animal models were made with carbon tetrachloride (CC14) mixed with vegetable oil (3/2, v/v), which was injected subcuta-neously twice a week for 6 weeks, and with 5% ethanol for free drinking water. At the same time, Rhein was administrated at the dose of 25mg/kg or 100mg/kg once a day for 6 weeks. The changes of both biochemical markers, such as the levels of alanine aminotransferase (ALT), hyaluronic acid (HA), procollagen type ffl (PCffl) in serum and SOD, malondialdehyde (MDA) in liver, and related histopathological parametres were determined. Results Compared with the model group, there were three kinds of changes in the larger quantity of rhein treated group. (l)The levels of ALT, HA, PC III in serum and MDA in liver homogenate were decreased significantly (from 150U/L+ 16U/L to 78U/L+ 18U/L, 321 ug/L+97 ug/L to 217ug/L+75ng/L, 31 ng/L + 14 ug/L to 16Ug/L+6ug/L and 3.67 nmol/mg+ 0.68 nmoymg to 1.8 mg + 0.34 nmol/mg, respectively, t> 2.977, P<0.01). However the level of SOD in liver was increased (from 62.45 NU/mg + 8.74NU/mg to 91.26NU/mg + 14.04NU/mg, t=4.453, P<0.01). (2)The expressions of transforming growth factor Bi (TGF-B1) and a-smooth muscle actin (a-SMA) in liver were markedly reduced (P<0.05 and P<0.01). (3)The collagen staining positive area was decreased and the grade of fibrosis was reduced significantly in liver (P<0.05 and P<0.01). Conclusions Rhein can protect hepatocyte from injury and prevent the progress of hepatic fibrosis in rats, which may associate with that rhein plays a role in antioxidation, anti-inflammation, inhibiting the expression of TGF-pi and suppressing the activation of hepatic stellate cells (HSCs).