摘要
目的研究红芪多糖(HPS)对ob/ob小鼠肝脂质氧化相关肝过氧化物酶体增殖物激活受体α(PPARα)、细胞色素P4502E1(CYP2E1)蛋白的影响。方法按照体重将雄性小鼠随机分为5组:模型组、对照组(硫辛酸30 mg·kg^(-1)·d^(-1))和高、中、低3个剂量实验组(HPS 200,100,50 mg·kg^(-1)·d^(-1)),各10只,1次/天,连续8周;同品系正常C57BL/6野生型雄性小鼠10只为正常组。用酶联免疫吸附法检测各组小鼠血清胆固醇(TC)、三酰甘油(TG)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量;逆转录-PCR(2^(-△△Ct)值)和蛋白质印迹法检测肝脂质氧化相关的PPARα和CYP2E1的基因和蛋白的表达。结果正常组、模型组、对照组和高、中、低3个剂量实验组的TC含量分别为(1.69±0.16),(3.97±0.34),(1.77±0.25),(1.86±0.63),(2.20±0.75)和(3.58±0.25)μmol·L^(-1);此6组的TG含量分别为(0.65±0.03),(1.32±0.04),(0.84±0.04),(0.86±0.04),(0.97±0.05)和(1.20±0.03)μmol·L^(-1);此6组的SOD含量分别为(0.20±0.03),(0.12±0.02),(0.20±0.03),(0.19±0.02),(0.14±0.03)和(0.13±0.03)μmol·L^(-1);此6组的MDA含量分别为(33.24±3.76),(53.77±2.17),(33.52±2.59),(35.23±3.52),(42.31±2.55)和(44.93±4.10)μmol·L^(-1);此6组的PPARα基因表达量分别为1.00±0.00,0.37±0.05,0.77±0.08,0.94±0.07,0.65±0.03和0.45±0.02;此6组肝组织中CYP2E1基因表达量分别为1.00±0.00,1.48±0.03,1.24±0.02,1.13±0.07,1.28±0.07和1.37±0.09。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.01);对照组和3个剂量实验组与模型组比较,差异均有统计学意义(均P<0.01)。蛋白表达结果的趋势与基因表达基本一致。结论 HPS可能通过调控PPARα表达,抑制CYP2E1,促进肝脂质氧化,减少脂质过氧化产物生成,提高机体抗氧化能力,从而改善ob/ob小鼠肝脂肪变性。
Objective To study the effect of Hedysarum polybotrys polysacchcaide(HPS) on peroxisome proliferator-activated receptors α(PPAR α)and cytochrome P450 2 E1(CYP2 E1) proteins related to lipid oxidation in the liver of ob/ob mice. Methods Male ob/ob mice were randomly divided into 5 groups according to weight: model group, positive control group(lipoic acid 30 mg·kg^(-1)) and high, medium and low dose experimental groups(HPS 200,100,50 mg·kg^(-1)) with 10 rats in each group, once a day for 8 weeks;10 non transgenic C57 BL/6 normal male mice were selected as normal group. Each group was given intragastric intervention continuously for 8 weeks. The contents of serum total cholesterol( TC), triglyceride( TG),superoxide dismutase( SOD) and malondialdehyde( MDA) were detected by enzyme linked immunosorbent assay. The expressions of PPAR α,CYP2 E1 mRNA and protein related to lipid oxidation in liver were detected by reverse transcription-PCR( 2^(-△△Ct)value) and Western blot. Results The contents of serum TC in normal group,model group,control group and high,medium,low dose experimental groups were( 1. 69 ± 0. 16),( 3. 97 ± 0. 34),( 1. 77 ± 0. 25),( 1. 86 ± 0. 63),( 2. 20 ± 0. 75) and( 3. 58 ± 0. 25) μmol · L^(-1);the contents of serum TG in the six groups were( 0. 65 ± 0. 03),( 1. 32 ± 0. 04),( 0. 84 ± 0. 04),( 0. 86 ± 0. 04),( 0. 97 ± 0. 05) and( 1. 20 ± 0. 03) μmol·L^(-1);the contents of SOD in the six groups were( 0. 20 ± 0. 03),( 0. 12 ± 0. 02),( 0. 20 ± 0. 03),( 0. 19 ± 0. 02),( 0. 14 ± 0. 03) and( 0. 13 ± 0. 03) μmol·L^(-1);the contents of MDA in the six groups were( 33. 24 ± 3. 76),( 53. 77 ± 2. 17),( 33. 52 ± 2. 59),( 35. 23 ± 3. 52),( 42. 31 ± 2. 55) and( 44. 93 ± 4. 10) μmol·L^(-1);the expression of PPARα gene in the six groups were 1. 00 ± 0. 00,0. 37 ± 0. 05,0. 77 ± 0. 08,0. 94 ± 0. 07,0. 65 ± 0. 03 and 0. 45 ± 0. 02,respectively;the expression of CYP2 E1 gene in the six groups were 1. 00 ± 0. 00,1. 48 ± 0. 03,1. 24 ± 0. 02,1. 13 ± 0. 07,1. 28 ± 0. 07 and 1
作者
张磊
金智生
金彩云
万生芳
李亚玲
杨晓轶
郇鹏飞
李圆
陈彦旭
ZHANG Lei;JIN Zhi-sheng;JIN Cai-yun;WAN Sheng-fang;LI Ya-ling;YANG Xiao-yi;HUAN Peng-fei;LI Yuan;CHEN Yan-xu(School of Basic Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Clinical College of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第9期1078-1082,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金地区基金资助项目(81660777)
甘肃中医药大学中青年科研基金资助项目(ZQ2017-13,ZQ2017-2)。
