芹菜素及其衍生物对高糖高脂诱导的非酒精性脂肪性肝病大鼠脂质代谢的影响

    Effects of Apigenin and Its Derivatives on Lipid Metabolism in Rats with Non-alcoholic Fatty Liver Disease Induced by High Glucose and Fat Diet

    • 摘要:
      目的  研究芹菜素及其4个衍生物A、B、C和D对NAFLD大鼠脂质代谢的影响。
      方法 利用高糖高脂饲料诱导大鼠NAFLD模型;HE和油红O染色观察芹菜素及其衍生物对NAFLD大鼠肝脏脂质沉积的影响;血清和组织生化、ELISA和Western Bloting观察芹菜素及其衍生物对NAFLD大鼠脂代谢相关指标TC、TG、LDL-c、FFA、Leptin、SREBP-1c、PPAR-α,以及氧化应激损伤相关指标SOD、MDA、GSH-px、CYP2E1、ALT、AST和TNF-α的影响。
      结果 芹菜素低浓度组及其衍生物C高低浓度组的肝重/体质量较模型组有所降低(P<0.05)。HE和油红O染色结果显示,芹菜素及其衍生物A、C和D肝脏脂肪变情况较模型组明显减轻。与模型组脂代谢相关指标相比,芹菜素衍生物A和D高低浓度组血清TC浓度降低(P<0.05或P<0.01);芹菜素及其衍生物A和D高低浓度组血清TG浓度降低(P<0.05或P<0.01或P<0.001);芹菜素及其衍生物A和B高低浓度组,衍生物C高浓度组和衍生物D低浓度组血清FFA浓度降低(P<0.05或P<0.01或P<0.001);芹菜素衍生物A低浓度组血清Leptin浓度降低(P<0.01);芹菜素高浓度组,芹菜素衍生物A和D低浓度组肝脏SREBP-1c浓度降低(P<0.05或P<0.001);芹菜素高浓度组,芹菜素衍生物A和D高低浓度组的PPAR-α浓度升高(P<0.05或P<0.001)。与模型组氧化应激和肝损伤相关指标相比,芹菜素衍生物A高浓度组的血清MDA浓度降低(P<0.01);芹菜素及其衍生物A和D的高低浓度组,芹菜素B和C低浓度组的血清TNF-α浓度降低(P<0.05或P<0.01或P<0.001);芹菜素及其衍生物A、C和D的高低浓度组血清ALT浓度降低(P<0.05或P<0.01或P<0.001);芹菜素衍生物A和B的低浓度组,芹菜素衍生物C的高低浓度组和芹菜素衍生物D高浓度组的血清AST浓度降低(P<0.05或P<0.01);芹菜素及其衍生物A和B高低浓度组,芹菜素衍生物C和D低浓度组的肝脏SOD浓度升高(P<0.05或P<0.001);芹菜素衍生物D高浓度组的肝脏GSH-Px浓度升高(P<0.05);芹菜素高浓度组和芹菜素衍生物A低浓度组的肝脏CYP2E1浓度降低(P<0.05或P<0.001)。
      结论 芹菜素及其衍生物A和D可通过调节大鼠脂质代谢过程以及缓解氧化应激和肝损伤程度而发挥抗NAFLD的作用,尤以芹菜素衍生物A的作用最优。

       

      Abstract:
      OBJECTIVE  To study the effects of apigenin and its four derivatives A, B, C and D on lipid metabolism in non-alcoholic fatty liverdisease(NAFLD) rats.
      METHODS  Established the NAFLD rat model induced by high sugar and fat diet. The effects of apigenin and its derivatives on hepatic steatosis of NAFLD rats were observed by HE and Oil Red O staining. Serum and tissue biochemistry, Elisa and WB were used to observe the effects of apigenin and its derivatives on the lipid metabolism of NAFLD rats, including TC, TG, HDL-c, LDL-c, FFA, Leptin, SREBP-1c and PPAR-α. And the effects of SOD, MDA, GSH-px, CYP2E1, ALT, AST and TNF-α on oxidative stress damage related indexes.
      RESULTS  The liver/body weight ratio in the low-concentration group of apigenin and the high-concentration group of its derivative C was lower than that in the model group(P<0.05). The HE and Oil Red O staining results indicated that the hepatic steatosis in the groups of apigenin and its derivatives A、C and D, was significantly alleviated compared with the model group. Compared with the lipid metabolism-related indicators in the model group, the serum TC concentrations in the high and low concentration groups of the apigenin derivatives A and D were decreased(P<0.05 or P<0.01); The serum triglyceride(TG) concentrations in the high and low concentration groups of apigenin and its derivatives A and D were significantly decreased(P<0.05 or P<0.01 or P<0.001). The serum FFA concentrations in the high and low concentration groups of apigenin and its derivatives A and B, the high concentration group of derivative C and the low concentration group of derivative D were all decreased(P<0.05 or P<0.01 or P<0.001); The serum Leptin concentration in the low-concentration group of derivative A was decreased(P<0.01). In the high-concentration group of apigenin and the low-concentration groups of apigenin derivatives A and D, the concentration of SREBP-1c in the liver decreased(P<0.05 or P<0.001). The concentrations of PPAR-α in the high-concentration group of apigenin and the low-concentration groups of apigenin derivatives A and D were increased(P<0.05 or P<0.001). Compared with the oxidative stress and liver injury-related indicators in the model group, the serum MDA concentration in the high-concentration group of apigenin derivative A was decreased(P<0.01); The serum TNF-α concentrations in the high and low concentration groups of apigenin and its derivatives A and D, as well as the low concentration groups of apigenin B and C, were decreased(P<0.05 or P<0.01 or P<0.001). The serum ALT concentrations in the high and low concentration groups of apigenin and its derivatives A, C and D were decreased(P<0.05 or P<0.01 or P<0.001); The serum AST concentrations in the low-concentration groups of derivatives A and B, the high-low concentration group of derivative C, and the high-concentration group of derivative D were all decreased(P<0.05 or P<0.01). The liver SOD concentrations in the high and low concentration groups of apigenin and its derivatives A and B, as well as the low concentration groups of derivatives C and D, were increased(P<0.05 or P<0.001); The concentration of GSH-Px in the liver of the high-concentration group of the derivative D increased(P<0.05); The liver CYP2E1 concentration in the high-concentration group of apigenin and the low-concentration group of apigenin derivative A was decreased(P<0.05 or P<0.001).
      CONCLUSION  Apigenin and its derivatives A and D can play an anti-NAFLD role by regulating lipid metabolism, alleviating oxidative stress and liver injury in rats, and apigenin derivative A has the best effect.

       

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