β-胡萝卜素对肝纤维化的防治作用

Oral β-carotene can reverse human liver fibrosis

目的:观察β-胡萝卜素防治肝纤维化的临床疗效.方法:63例肝纤维化患者,按病理分期S0-S1期31例,S2-S4期32例.口服β-胡萝卜素,放射免疫分析法测定治疗前后血清透明质酸(HA)、层粘蛋白(LN)、Ⅳ型前胶原(Ⅳ-C),Ⅲ型前胶原肽(PCⅢ),ELISA法测定血清结缔组织生长因子(CTGF)、血小板衍生生长因子-BB(PDGF-BB)、金属蛋白酶抑制剂-1(TIMP-1)、转化生长因子-β1(TGF-β1),免疫组织化学检查Ⅳ型胶原及Ⅱ型胶原,并与60例正常人对照分析.结果:β胡萝卜素治疗前后,肝纤维化S0-S1、S2-S4期患者HA、LN、Ⅳ-C、PCⅢ有统计学差异(S0-S1:t=4.917,2.120,3.138,3.583,P<0.01或0.05;S2-S4:t=5.963,5.563,9.162,4.972,均P<0.01).S2-S4期患者与正常人比较HA、Ⅳ-C有统计学差异(均P<0.01).治疗前后肝纤维化S0-S1、S2-S4期患者CTGF、PDGF-BB、TIMP-1、TGF-β1均有统计学差异(S0-S1:t=4.176,2.683,2.098,2.045,P<0.01或0.05;S2-S4:t=4.792,7.519,2.877,2.305,均P<0.01).S2-S4期患者与正常人比较CTGF、PDGF-BB有统计学差异(均P<0.01).免疫组织化学检测结果表明,免疫组织化学检查口服β-胡萝卜素后S4期患者病情有所改善.结论:口服β-胡萝卜素,通过调节肝星状细胞的功能,对S0-S1、S2-S4期患者均有逆转肝纤维化的作用,是一种很有前景的抗肝纤维化药物.

AIM： To observe the clinical efficacy of β-carotene in the treatment of patients with liver fibrosis. METHODS： Sixty-three patients with liver fibrosis were divided into two groups according to pathological stage： patients with S0-S1 liver fibrosis （n = 31） and those with S2-S4 disease （n = 32）. Oral β-carotene was given to all the patients. Sixty healthy volunteers were used as controls. Serum hyaluronic acid （HA）, laminin （LN）, type IV collagen （IV-C）, procollagen III （PCIII）, connective tissue growth factor （CTGF）, plateletderived growth factor-BB （PDGF-BB）, tissue inhibitor of metalloproteinase-1 （TIMP-1）, andtransforming growth factor-β1 （TGF-β1） in these subjects were measured by radioimmunoassay and enzyme-linked immunosorbent assay. Immunohistochemistry for IV-C was also performed. RESULTS： Serum HA, LN, IV-C and PC III showed significant differences in patients with both S0-S1 and S2-S4 liver fibrosis between before and after β-carotene treatment （S0-S1： t = 4.917, 2.120, 3.138, 3.583, P 0.01 or 0.05; S2-S4： t = 5.963, 5.563, 9.162, 4.972, all P 0.01）. Serum HA and IV-C were statistically significant between patients with S2-S4 liver fibrosis after β-carotene treatment and normal controls （both P 0.01） Serum CTGF, PDGF-BB, TIMP-1 and TGF-β1 showed significant differences between in patients with both S0-S1 and S2-S4 liver fibrosis between before and after β-carotene treatment （S0-S1： t = 4.176, 2.683, 2.098, 2.045, P 0.01 or 0.05; S2-S4： t = 4.792, 7.519, 2.877, 2.305, all P 0.01）. Serum CTGF and PDGF-BB were statistically significant between patients with S2-S4 liver fibrosis after β-carotene treatment and normal controls （both P 0.01）. Immunohistochemistry analysis showed that oral β-carotene could improve hepatic fibrosis even in patients with S4 disease. CONCLUSION： Oral β-carotene can reverse human hepatic fibrosis by regulating the function of hepatic stellate cells and represents a promising anti-hepatic fibrosis drug.