摘要目的 探讨芹菜素对非酒精性脂肪性肝炎(NASH)大鼠肝组织过氧化物酶体增殖物激活受体(PPARs)表达的影响. 方法 采用高脂饲料喂养的方法复制大鼠NASH模型,成模后分为正常组,模型组,多烯磷脂酰胆碱组,芹菜素低剂量组、中剂量组和高剂量组.实验结束后,进行胰岛素敏感性测定;腹腔静脉取血测定生物化学指标ALT、AST、总胆固醇(TC)、总甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)和空腹胰岛素(FINS);计算肝指数和胰岛素抵抗指数(HOMA-IR);提取肝组织,运用免疫组织化学和RT-PCR测定各组大鼠肝组织PPAR α 、PPAR γ蛋白和mRNA表达情况.多组间的比较采用单因素方差分析.结果 胰岛素敏感性的变化:各组之间差异均有统计学意义,两两比较结果显示,正常组明显高于其他组,而芹菜素组高于模型组,尤其是高剂量组;生物化学指标检测结果显示:与模型组ALT[(163.1±15.5) U/L、AST (284.6±23.5) U/L]活性和TC[(2.23±0.76)mmol/L]、TG[(1.94±0.33) mmol/L]、LDL-C[(2.63±0.18) mmol/L]、HDL-C[(0.77±0.51)mmol/L]、FBG[(8.64±1.02) mmol/L]和FINS[(3.48±1.41) U/L]含量相比,芹菜素组尤其是高剂量组能减少ALT [(95.4±7.3)U/L]、AST [(183.7±14.3)U/L]活性和TC [(1.61±0.25)mmol/L]、TG[(1.23土0.21) mmol/L、LDL-C[(1.86±0.13) mmol/L、FBG[(5.29±1.45)mmol/L和FINS[(0.76±0.86) U/L]的含量,升高HDL-C[(1.04±0.17) mmol/L]的含量;与模型组大鼠肝指数(3.75±0.25)和HOMA-IR (1.34±0.06)相比,芹菜素组尤其是高剂量组能够显著减低肝指数(2.90±0.17)和HOMA-IR(0.18土0.04,P＜0.05);免疫组织化学染色和RT-PCR结果显示:与模型组相比,芹菜素组PPAR α 、PPARγ蛋白和mRNA表达增加,尤其是高剂量组,PPAR α 蛋白和mRNA相对表达量分别为18.27±4.05和0.63±0.02,PPAR γ蛋白和mRNA相对表达量分别为8.48±5.05和0.39±0.02,P＜0.05. 结论 芹菜素能改善胰岛素抵抗和糖脂代谢,减轻肝脏脂肪变性和炎症坏死,降低血清TC、TG、LDL-C、FBG、FINS和HOMA-IR水平,提高HDL-C水平,推测其可能对大鼠NASH具有保护作用.

abstractsObjective To investigate the effect of apigenin on the protein expression levels of peroxisome proliferator-activated receptors (PPARs) in liver tissues of rats with nonalcoholic steatohepatitis (NASH).Methods The NASH rat model was established by feeding of a high-fat diet.Unmodeled rats served as the normal controls.The modeled rats were divided into a model control group,Essentiale treatment group (300 mg/kg/day),and three apigenin treatment groups for low-dose (15 mg/kg/day),moderate-dose (30 mg/kg/day) and high-dose (60 mg/kg/day).After 13 weeks of treatment,changes in insulin sensitivity from pre-treatment baseline were assessed by measuring the alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglycerides (TG),low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C),fasting blood glucose (FBG) and fasting insulin (FINS).The liver index and HOMA-IR were also calculated.Protein and gene expression of PPARa and PPARγ in liver tissue were assessed by immunohistochemistry and RT-PCR.Statistical analysis was performed by the LSD test and Games-Howell test.Results The apigenintreated groups showed a significantly greater change in insulin sensitivity than the untreated model group,with the most significant change occurring in the high-dose group (P ＜ 0.05).Compared with the untreated model group,the apigenin-treated groups showed lower levels of ALT (95.4±7.3),AST (183.7±14.3),TC (1.61±0.25),TG (1.23±0.21),LDL-C (1.86±0.14),FBG (5.29±1.45) and FINS (0.76±0.86),but a higher level of HDL-C (1.04±0.17); again,the high-dose group showed the greatest change (all P ＜ 0.05).Compared to the untreated model group,the apigenin-treated groups showed significantly lower liver index (3.75±0.25 vs.2.90±0.17) and HOMA-IR (1.34±0.06 vs.0.18±0.04),with the high-dose group showing the greatest change (both P ＜ 0.05).Compared to the untreated model group,the apigenin-treated groups showed higher levels of protein and mRNA of PPARα (18.27±4.05 and 0.63±0.02,respectively) and PPARγ(8.48±5.05 and 0.39±0.02),with the high-dose group showing the greatest change (all P ＜ 0.05).Conclusion Apigenin can improve glucose tolerance,lipid metabolism and insulin resistance while decreasing blood levels of TC,TG,LDL-C,FBG,FINS and HOMA-IR,and increasing HDL-C in NASH,as shown in a high-fat diet induced rat model,and may have therapeutic potential.