姜黄素对四氯化碳诱导肝纤维化大鼠肝组织TGF-β1及Caspase-3表达的影响

Effects of curcumin on expression of TGF-β1 and Caspase-3 in hepatic fibrotic rats induced by Carbon Tetrachoride

目的:观察姜黄素(Cur)对四氯化碳诱导大鼠肝纤维化及对其肝组织转化生长因子-β1(TGF-β1)及半胱天冬酶-3(Caspase-3)表达的影响.方法:采用皮下注射400g/L四氯化碳复制模型,造模后给予姜黄素治疗,观察肝组织病理改变并进行肝纤维化分级和血清生化学检测;免疫组化法测定肝组织中TGF-β1及Caspase-3蛋白表达的变化,RT-PCR检测肝组织中TGF-β1mRNA表达.结果:Cur治疗组大鼠肝纤维化程度较模型组显著减轻(P<0.01);并且大鼠血清ALT(nkat/L),AST(nkat/L),ALP(nkat/L)水平明显降低[(757±234)vs(1677±252),(2776±238)vs(4865±403),(1850±191)vs(4310±728),P<0.05或P<0.01],A/G比值提高[(0.89±8.06)vs(0.60±7.48),P<0.05];Cur治疗组TGF-β1mRNA,TGF-β1表达较模型组显著下降[(3.13±1.55)vs(9.56±2.01),(0.32±0.12)vs(0.87±0.40),P<0.05或P<0.01];Caspase-3表达较模型组显著升高[(5.47±1.06)vs(1.56±0.61),P<0.05].结论:Cur对四氯化碳诱导的大鼠肝纤维化具有显著的治疗作用,其作用机制可能与抑制TGF-β1表达、促进Caspase-3表达相关.

AIM： To investigate the effects of curcumin on expression of TGF-β1 and Caspase-3 in the fibrotic liver induced by Carbon Tetrachoride in rats. METHODS： The liver fibrosis models induced by CC14 were established in rats and they were treated with curcumin. Liver fibrosis grades were evaluated on the liver tissue sections and biochemical examinations were performed. Immunohistochemistry was performed to detect the expression of transforming growth factor β1 （TGF-β1） and Caspase-3 and reverse transcriptase polymerase chain reaction （RT-PCR） was performed to detect mRNA expression of TGF--β1. RESULTS： The grade of liver fibrosis in curcumin group was obviously lower compared with that in model group （P 〈 0.01 ）. Compared with those in model control group, the serum ALT, AST and ALP levels were depressed in curcumin group （757.15 ± 233.88 vs 1676.50 ± 252.38, 2775.56 ± 237.88 vs 4865.14 ± 402.91, 1850.37 ± 190.87 vs 4310.03 ± 727.81, P 〈0.05 or P 〈0.01） , while the values of A/G were enhanced （0.89 ± 8.06 vs0. 60 ± 7.48, P 〈 0.05 ）. Compared with those in model control group, the expressions of TGF-β1 protein and TGF-β1 mRNA in liver were significantly reduced in curcumin group（3.13 ±1.55 vs 9.56±2.01, 0.32 ±0.12 vs 0. 87 ±0.40 P 〈0.05 or P 〈0.01 ）, while the expression of Caspase-3 in liver was significantly enhanced （5.47 ± 1.06 vs 1.56 ± 0.61, P 〈 0.05 ）. CONCLUSION： Cureumin has obvious therapeutic effects on the experimental liver fibrosis induced by Carbon Tetrachoride in rats. The mechanism possibly involves the inhibition of TGF-β1 and enhanced expression of Caspase-3.