Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL...Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL particles. ABCA1 may act as a phospholipid translocase facilitating p hospholipid binding to apoA-I. ABCA1 gene expression is upregulated in cholester ol-loaded cells as a result of activation of LXR/RXR-mediated gene transcription . LXR and RXR coordinately induce a battery of genes mediating cellular choleste rol efflux, centripetal cholesterol transport, and cholesterol excretion in bile . Small-molecule activators of LXR/RXR or other stimulators of macrophage or int estinal cholesterol efflux hold great promise as future treatments for atheroscl erosis.展开更多
目的:研究蓝靛果花色苷对高脂血症大鼠肝脏低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、三磷酸腺苷结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)及ABCA1基因表达的影响。方法:选择2月龄雄性Wistar大鼠60...目的:研究蓝靛果花色苷对高脂血症大鼠肝脏低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、三磷酸腺苷结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)及ABCA1基因表达的影响。方法:选择2月龄雄性Wistar大鼠60只,将大鼠随机分为6组,分别为基础饲料对照组(ND,1.2 g/(kg·dm_b)生理盐水灌胃)、高脂模型对照组(HFD,1.2 g/(kg·dm_b)生理盐水灌胃)、阳性对照组(10 mg/(kg·dm_b)辛伐他汀片灌胃),蓝靛果花色苷低、中、高剂量组(HFD+L、HFD+M、HFD+H,分别给予4.0、40.0、120.0 mg/(kg·dm_b)的花色苷灌胃),持续28 d。实验结束后,测定血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、载脂蛋白A(apolipoprotein A,Apo-A)及载脂蛋白B(Apo-B)等血脂指标水平。取大鼠肝脏,利用实时荧光定量聚合酶链式反应测定大鼠肝脏组织中LDLR、ABCG1、ABCA1 m RNA表达量,Western blot检测LDLR蛋白表达水平。结果:蓝靛果花色苷干预后,与HFD组相比,花色苷均能不同程度地降低高血脂大鼠血清中TC、TG、LDL-C、Apo-B的含量(P<0.05或P<0.01),显著升高HDL-C及Apo-A的含量(P<0.05或P<0.01)。花色苷各剂量组LDLR蛋白和m RNA水平均增高,与HFD组比较差异有显著性(P<0.05),ABCA1 m RNA和ABCG1 m RNA的表达水平也高于HFD组,尤其是花色苷中、高剂量组差异明显(P<0.05)。结论:40.0 mg/(kg·dm_b)蓝靛果花色苷具有明显的调节血脂作用,其作用机制可能是通过上调肝脏LDLR和ABC家族基因的表达,进而调节胆固醇逆转运过程。展开更多
文摘Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL particles. ABCA1 may act as a phospholipid translocase facilitating p hospholipid binding to apoA-I. ABCA1 gene expression is upregulated in cholester ol-loaded cells as a result of activation of LXR/RXR-mediated gene transcription . LXR and RXR coordinately induce a battery of genes mediating cellular choleste rol efflux, centripetal cholesterol transport, and cholesterol excretion in bile . Small-molecule activators of LXR/RXR or other stimulators of macrophage or int estinal cholesterol efflux hold great promise as future treatments for atheroscl erosis.
文摘目的:研究蓝靛果花色苷对高脂血症大鼠肝脏低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、三磷酸腺苷结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)及ABCA1基因表达的影响。方法:选择2月龄雄性Wistar大鼠60只,将大鼠随机分为6组,分别为基础饲料对照组(ND,1.2 g/(kg·dm_b)生理盐水灌胃)、高脂模型对照组(HFD,1.2 g/(kg·dm_b)生理盐水灌胃)、阳性对照组(10 mg/(kg·dm_b)辛伐他汀片灌胃),蓝靛果花色苷低、中、高剂量组(HFD+L、HFD+M、HFD+H,分别给予4.0、40.0、120.0 mg/(kg·dm_b)的花色苷灌胃),持续28 d。实验结束后,测定血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、载脂蛋白A(apolipoprotein A,Apo-A)及载脂蛋白B(Apo-B)等血脂指标水平。取大鼠肝脏,利用实时荧光定量聚合酶链式反应测定大鼠肝脏组织中LDLR、ABCG1、ABCA1 m RNA表达量,Western blot检测LDLR蛋白表达水平。结果:蓝靛果花色苷干预后,与HFD组相比,花色苷均能不同程度地降低高血脂大鼠血清中TC、TG、LDL-C、Apo-B的含量(P<0.05或P<0.01),显著升高HDL-C及Apo-A的含量(P<0.05或P<0.01)。花色苷各剂量组LDLR蛋白和m RNA水平均增高,与HFD组比较差异有显著性(P<0.05),ABCA1 m RNA和ABCG1 m RNA的表达水平也高于HFD组,尤其是花色苷中、高剂量组差异明显(P<0.05)。结论:40.0 mg/(kg·dm_b)蓝靛果花色苷具有明显的调节血脂作用,其作用机制可能是通过上调肝脏LDLR和ABC家族基因的表达,进而调节胆固醇逆转运过程。
基金supported by grants from The National Natural Science Foundation of China(30570754)The Fund of the Department of Education of Hunan Province(08C746)The Fund for Bring New Ideal of Central South University(ZRE52)~~
