Shi Tingting, Zhuang Rangxiao, Zhou Hongping, Wang Fugen, Shao Yidan, Cai Zhaobin
The Xixi Hospital of Zhejiang Chinese Medical University, Hangzhou 310023, China.
Zhonghua Gan Zang Bing Za Zhi. 2015 Feb;23(2):124-9. doi: 10.3760/cma.j.issn.1007-3418.2015.02.010.
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).
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 PPARα and PPARgamma in liver tissue were assessed by immunohistochemistry and RT-PCR.Statistical analysis was performed by the LSD test and Games-Howell test.
The apigenin-treated 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 less than 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 less than 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 less than 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 PPARgamma(8.48+/-5.05 and 0.39+/-0.02),with the high-dose group showing the greatest change (all P < 0.05).
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.
研究芹菜素对非酒精性脂肪性肝炎（NASH）大鼠肝组织中过氧化物酶体增殖物激活受体（PPARs）蛋白表达水平的影响。
通过高脂饮食建立NASH大鼠模型。未建模的大鼠作为正常对照。将建模大鼠分为模型对照组、易善力治疗组（300mg/kg/天）以及三个芹菜素治疗组，分别为低剂量组（15mg/kg/天）、中剂量组（30mg/kg/天）和高剂量组（60mg/kg/天）。治疗13周后，通过测量丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）、甘油三酯（TG）、低密度和高密度脂蛋白胆固醇（LDL-C和HDL-C）、空腹血糖（FBG）和空腹胰岛素（FINS）来评估治疗前基线胰岛素敏感性的变化。还计算了肝脏指数和HOMA-IR。通过免疫组织化学和RT-PCR评估肝组织中PPARα和PPARγ的蛋白和基因表达。采用LSD检验和Games-Howell检验进行统计分析。
芹菜素治疗组的胰岛素敏感性变化显著大于未治疗的模型组，高剂量组变化最为显著（P<0.05）。与未治疗的模型组相比，芹菜素治疗组的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）和FINS（0.76±0.86）水平较低，但HDL-C水平较高（1.04±0.17）；同样，高剂量组变化最大（所有P<0.05）。与未治疗的模型组相比，芹菜素治疗组的肝脏指数（3.75±0.25对2.90±0.17）和HOMA-IR（1.34±0.06对0.18±0.04）显著较低，高剂量组变化最大（均P<0.05）。与未治疗的模型组相比，芹菜素治疗组的PPARα蛋白和mRNA水平较高（分别为18.27±4.05和0.63±0.02）以及PPARγ（8.48±5.05和0.39±0.02），高剂量组变化最大（所有P<0.05）。
在高脂饮食诱导的大鼠模型中，芹菜素可改善NASH大鼠的糖耐量、脂质代谢和胰岛素抵抗，同时降低血液中TC、TG、LDL-C、FBG、FINS和HOMA-IR水平，提高HDL-C水平，可能具有治疗潜力。
