基于PPARα信号通路探究蓝刺头黄酮对高脂血症大鼠的降血脂作用

Hypolipidemic effect of flavonoids in hyperlipidaemic rats and study of PPARαpathway in blue prickly head flavonoids

将50只8周龄雄性高脂血症SD大鼠随机分为5组,每组10只。按蓝刺头黄酮(total flavonoids from echinops latifolius tausch,TFET)剂量,分别设高剂量组(200 mg/kg)、中剂量组(100 mg/kg)、低剂量组(50 mg/kg)、阳性对照组(辛伐他汀20 mg/kg)和模型组(灌胃蒸馏水0.8 mL/d,并给予给予高脂鼠粮),连续给药45 d。另取10只8周龄健康雄性SD大鼠作为空白对照组,灌胃蒸馏水0.8 mL/d,同时给予普通鼠粮。试验过程中,模型组、阳性对照组、TFET各剂量组大鼠给予高脂鼠粮,对照组大鼠给予普通鼠粮。对各组大鼠分别连续45 d灌服相应浓度的TFET、辛伐他汀和蒸馏水,并检测大鼠相关血脂生化指标、抗氧化指标和PPARα通路相关基因表达量。结果显示,高剂量TFET能极显著降低TC、TG、LDL-C含量,并极显著提高HDL-C含量;中剂量TFET能极显著降低TC、TG含量,显著降低LDL-C含量;低剂量TFET能显著降低TC、LDL-C含量。高、中、低剂量TFET均能极显著降低提高SOD活性;高、中剂量TFET能极显著降低MDA含量;高剂量TFET能极显著提高T-AOC活性。高剂量的TFET能极显著提高大鼠肝脏中PPARα、CYP7A1、CPT-1基因表达量;中剂量的TFET能显著提高CYP7A1、CPT-1基因表达量,能显著提高PPARα基因的表达量;低剂量的TFET能极显著提高CYP7A1基因表达量,显著提高CPT-1基因表达量。结果表明,TFET对高脂血症大鼠具有抗氧化和降血脂的作用,其机制可能与通过激活PPARα及其下游相关基因促进脂肪酸β氧化有关。

Hyperlipidaemic rats were randomly divided into a model group,a total flavonoids from echinops latifolius tausch(TFET)high,medium and low dose group,and a positive control group;meanwhile,healthy rats were selected as a blank control group.The rats in each group were dosed with the corresponding concentrations of TFET,simvastatin and distilled water for 45 consecutive days,and were tested for relevant lipid biochemical indexes,antioxidant indexes and PPARαpathway-related gene expression.The results showed that high-dose TFET could reduce the concentrations of TC,TG and LDL-C and increase the concentration of HDL-C very significantly;medium-dose TFET could reduce the concentrations of TC and TG very significantly and reduce the concentration of LDL-C significantly;and low-dose TFET could reduce the concentrations of TC and LDL-C significantly.High,medium and low doses of TFET can extremely significantly reduce increase SOD activity;high and medium doses of TFET can extremely significantly reduce MDA content;high dose of TFET can extremely significantly increase T-AOC activity.The high dose of TFET could extremely significantly increase the expression of PPARα,CYP7A1and CPT-1genes in rat liver;the medium dose of TFET could extremely significantly increase the expression of CYP7A1and CPT-1genes,and could significantly increase the expression of PPARαgene;the low dose of TFET could extremely significantly increase the expression of CYP7A1gene,and significantly increase the CPT-1gene expression.The results suggest that TFET has antioxidant and lipid-lowering effects on hyperlipidaemic rats,and its mechanism may be related to the activation of PPARαand its downstream related genes to promote fatty acidβ-oxidation.