乌药叶提取物对高脂血症模型大鼠降脂作用以及肝脏LKB1-AMPK通路的影响

Effect of Lindera Aggregata Extract on Lipid-lowering and Hepatic LKB1-AMPK Pathway in Hyperlipidemic Rat Model

目的考察乌药叶提取物对高脂血症大鼠模型降血脂作用以及对肝脏LKB1-AMPK通路相关蛋白表达的影响。方法采用高脂饲料诱导的混合型高脂血症大鼠模型,以高、低剂量(1.6,0.8 g·kg^-1以生药量计)的乌药叶提取物灌胃,阳性药组给予非诺贝特20 mg·kg^-1,连续8周。分别在4,8周后检测血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平。实验末处死大鼠,解剖取肝脏,计算肝脏指数,油红O染色观察肝组织脂质蓄积程度,Western blotting检测肝脏LKB1-AMPK通路相关蛋白的表达。结果连续给药4周,与模型组相比,阳性药组血清TG水平有显著降低(P<0.05)。连续给药8周,与模型组相比,高剂量组能显著降低血清中TC、TG、LDL-C的水平(P<0.01或P<0.05)。与对照组比,高、低剂量组和模型组肝脏指数均极显著升高(P<0.01);与模型组比,高、低剂量组有降低的趋势,但差异无统计学意义。肝组织油红O染色结果显示,模型组肝细胞脂质蓄积严重,脂肪变性程度高,高剂量组肝细胞脂质蓄积和脂肪变性程度均有不同程度的改善。高、低剂量组均可显著提高模型大鼠肝脏AMPKα蛋白磷酸化水平。结论乌药叶提取物能够降低血清脂质水平,改善肝细胞脂质蓄积,并且增加AMPKα蛋白磷酸化水平,激活AMPKα,从而促进脂质代谢。

OBJECTIVE To study the antilipemic function of extract from Lindera aggregata and the effect on hepatic LKB1-AMPK pathway in hyperlipidemia model rats.METHODS A rat model of mixed hyperlipidemia induced by high-fat diet,high and low doses group were administered with high and low doses of 1.6,0.8 g·kg^-1 of crude drug extracts for 8 weeks.The positive group was administered with 20 mg·kg^-1 fenofibrate.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)were detected after 4 and 8 weeks administration.At the end of the experiment,the rats were sacrificed and the liver was dissected to observe its effect on liver index and the degree of lipid accumulation in liver tissues was observed by oil red O staining.Western blotting was used to detect the expression of LKB1-AMPK pathway related proteins in liver.RESULTS After continuous administration for 4 weeks,compared with the model group,the levels of TG in serum significantly reduced in the positive group(P<0.05).After continuous administration for 8 weeks,the high dose group significantly reduced the levels of TC and LDL-C in serum compared with the model group(P<0.01 or P<0.05).Compared with the control group,the liver index of the high and low dose groups and the model group were extremely significantly increased(P<0.01).Compared with the model group,the high and low dose groups had a decreasing trend,but there was no statistical difference.The results of oil red O staining in liver tissue showed that the hepatocytes in the model group had serious lipid accumulation and high degree of steatosis,and the hepatocytes in the high dose group of Lindera aggregata extract had different degrees of improvement in lipid accumulation and steatosis.The high and low dose group,AMPKαprotein phosphorylation was significantly increased in rats liver.CONCLUSION Lindera aggregata extract has certain lipid-lowering effect and can improve hepatocyte steatosis.The mechanism may promote lipid metabolism by activating AMPKαprotein phosphorylation.