Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipo...Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipopolysaccharides.In addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune responses.It modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic inflammation.In addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune responses.This modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 subtype.This novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).展开更多
End stage-renal-disease (ESRD) is associated with dyslipidemia and premature atherosclerosis. The study evaluates the effect of hemodialysis (HD) on HDL-remodeling between pre- and post-HD. Was conducted a cross-secti...End stage-renal-disease (ESRD) is associated with dyslipidemia and premature atherosclerosis. The study evaluates the effect of hemodialysis (HD) on HDL-remodeling between pre- and post-HD. Was conducted a cross-sectional study with 50 ESRD male patients, undergoing HD at Ana Neri Hospital, Salvador, Brazil. All individuals were on HD for at least 3 months, into a three sessions protocol for 3 - 4 hours per week, with a polysulfone low-flow basic-dialyzing-membrane and unfractionated-heparin. HDL Phospholipid-incorporation was measured by 14C-PL-scintillation-counting, expressed as %14C-PL/mL/hour. Paraoxonase (PON-1) activity was measured by spectrophotometry using paraoxon as substrate. Cardiovascular risk ratios and atherogenic index of plasma were calculated. Total cholesterol, HDL-C and non-HDL-C increased at post-HD on all age groups, but without triglycerides (TG) changes. TG/HDL-C decreased in 30 - 39 and 40 - 49 year (y) at post-HD (p 0.05). LDL-C/apoB increased in >60 y, after HD (p < 0.05). HDL-C/apo-AI increased in 40 - 49 y (p 0.05) and >60 (p 0.01). On the other hand, non-HDL-C/HDL-C reduced in 40 - 49 and >60 y, at post-HD (p 0.05). The linear-correlation between %14C-PL-incorporation and non-HDL-C/HDL-C was negative in 30 - 39 y, both at pre-HD (r = -0.90;p = 0.002) and post-HD (r = -0.78;p = 0.022). Linear-correlation between PON-1 and %14C-PL-incorporation was positive in >60 y, both at pre- (r = 0.63;p = 0.029) and post-HD (r = 0.65;p = 0.022). PON-1 activity increased at pre- (59 ± 30) and post-HD (73 ± 38) in 50 - 59 y (p 0.05). The %14C-PL-incorporation was reduced in >60 y (p 0.05), when compared to pre- and post-HD. ESRD patients undergoing HD shows important changes on lipid-profile, PON-1-activity, cardiac risk ratios and HDL-remodeling. These results demonstrate the influence of HD with a polysulfone low-flow basic-dialyzing-membrane and unfractionated-heparin on lipoprotein metabolism.展开更多
[目的]观察五苓散对高脂血症(hyperlipidemia,HLP)小鼠的干预作用,探讨其可能的作用机制。[方法]48只雄性ICR小鼠随机分为正常组,模型组,依折麦布组,五苓散低、中、高剂量组。除正常组外,均采用高脂饲料喂养,药物干预组造模的同时分别...[目的]观察五苓散对高脂血症(hyperlipidemia,HLP)小鼠的干预作用,探讨其可能的作用机制。[方法]48只雄性ICR小鼠随机分为正常组,模型组,依折麦布组,五苓散低、中、高剂量组。除正常组外,均采用高脂饲料喂养,药物干预组造模的同时分别给予依折麦布、五苓散干预,连续8周。实验期间,观察各小鼠一般体征,检测血清总胆固醇(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)、总胆汁酸(total bile acid,TBA)水平;苏木精-伊红(hematoxylin-eosin,HE)染色、油红O染色检测肝组织脂质沉积情况;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)试剂盒检测小鼠磷脂转运蛋白(phospholipid transfer protein,PLTP)、胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)表达;免疫组化检测肝脏中胆固醇7α羟化酶(cholesteral 7α-hydroxylase,CYP7A1)表达,超高效液相色谱仪串联三重四极杆质谱仪(ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer,UPLC-MS/MS)靶向检测肝组织胆汁酸(bile acid,BAs)水平,并进行质谱多反应监测分析,荧光分析肠道胆汁酸受体(Takeda G protein-coupled receptor 5,TGR5)和法尼醇X受体(farnesoid X receptor,FXR1)表达。[结果]五苓散能抑制HLP小鼠体质量增加。在实验第4周,低剂量五苓散显著降低HLP小鼠TC水平(P<0.01),各剂量五苓散显著降低HLP小鼠TG水平(P<0.01);实验第8周,高剂量五苓散升高HLP小鼠TG水平(P<0.05),但对TC、HDL-C、LDL-C表达水平的改善不明显(P>0.05)。五苓散减少HLP小鼠肝细胞脂肪空泡及脂滴数量。中、高剂量五苓散上调HLP小鼠PLTP水平(P<0.01),低、高剂量五苓散上调小鼠CETP水平(P<0.05,P<0.01),降低血清TBA水平,升高CYP7A1的表达水平(P<0.01),并逆转高脂饮食引起的BAs代谢紊乱,同时抑制肠道的TGR5和FXR1表达。[结论]五苓散能降低高脂饮食诱导的HLP小鼠血脂水平,该作用与上调CETP和PLTP的水平,促进胆固醇的逆转运及肝脏BAs代谢有关。展开更多
文摘Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipopolysaccharides.In addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune responses.It modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic inflammation.In addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune responses.This modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 subtype.This novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).
文摘End stage-renal-disease (ESRD) is associated with dyslipidemia and premature atherosclerosis. The study evaluates the effect of hemodialysis (HD) on HDL-remodeling between pre- and post-HD. Was conducted a cross-sectional study with 50 ESRD male patients, undergoing HD at Ana Neri Hospital, Salvador, Brazil. All individuals were on HD for at least 3 months, into a three sessions protocol for 3 - 4 hours per week, with a polysulfone low-flow basic-dialyzing-membrane and unfractionated-heparin. HDL Phospholipid-incorporation was measured by 14C-PL-scintillation-counting, expressed as %14C-PL/mL/hour. Paraoxonase (PON-1) activity was measured by spectrophotometry using paraoxon as substrate. Cardiovascular risk ratios and atherogenic index of plasma were calculated. Total cholesterol, HDL-C and non-HDL-C increased at post-HD on all age groups, but without triglycerides (TG) changes. TG/HDL-C decreased in 30 - 39 and 40 - 49 year (y) at post-HD (p 0.05). LDL-C/apoB increased in >60 y, after HD (p < 0.05). HDL-C/apo-AI increased in 40 - 49 y (p 0.05) and >60 (p 0.01). On the other hand, non-HDL-C/HDL-C reduced in 40 - 49 and >60 y, at post-HD (p 0.05). The linear-correlation between %14C-PL-incorporation and non-HDL-C/HDL-C was negative in 30 - 39 y, both at pre-HD (r = -0.90;p = 0.002) and post-HD (r = -0.78;p = 0.022). Linear-correlation between PON-1 and %14C-PL-incorporation was positive in >60 y, both at pre- (r = 0.63;p = 0.029) and post-HD (r = 0.65;p = 0.022). PON-1 activity increased at pre- (59 ± 30) and post-HD (73 ± 38) in 50 - 59 y (p 0.05). The %14C-PL-incorporation was reduced in >60 y (p 0.05), when compared to pre- and post-HD. ESRD patients undergoing HD shows important changes on lipid-profile, PON-1-activity, cardiac risk ratios and HDL-remodeling. These results demonstrate the influence of HD with a polysulfone low-flow basic-dialyzing-membrane and unfractionated-heparin on lipoprotein metabolism.
文摘[目的]观察五苓散对高脂血症(hyperlipidemia,HLP)小鼠的干预作用,探讨其可能的作用机制。[方法]48只雄性ICR小鼠随机分为正常组,模型组,依折麦布组,五苓散低、中、高剂量组。除正常组外,均采用高脂饲料喂养,药物干预组造模的同时分别给予依折麦布、五苓散干预,连续8周。实验期间,观察各小鼠一般体征,检测血清总胆固醇(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)、总胆汁酸(total bile acid,TBA)水平;苏木精-伊红(hematoxylin-eosin,HE)染色、油红O染色检测肝组织脂质沉积情况;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)试剂盒检测小鼠磷脂转运蛋白(phospholipid transfer protein,PLTP)、胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)表达;免疫组化检测肝脏中胆固醇7α羟化酶(cholesteral 7α-hydroxylase,CYP7A1)表达,超高效液相色谱仪串联三重四极杆质谱仪(ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer,UPLC-MS/MS)靶向检测肝组织胆汁酸(bile acid,BAs)水平,并进行质谱多反应监测分析,荧光分析肠道胆汁酸受体(Takeda G protein-coupled receptor 5,TGR5)和法尼醇X受体(farnesoid X receptor,FXR1)表达。[结果]五苓散能抑制HLP小鼠体质量增加。在实验第4周,低剂量五苓散显著降低HLP小鼠TC水平(P<0.01),各剂量五苓散显著降低HLP小鼠TG水平(P<0.01);实验第8周,高剂量五苓散升高HLP小鼠TG水平(P<0.05),但对TC、HDL-C、LDL-C表达水平的改善不明显(P>0.05)。五苓散减少HLP小鼠肝细胞脂肪空泡及脂滴数量。中、高剂量五苓散上调HLP小鼠PLTP水平(P<0.01),低、高剂量五苓散上调小鼠CETP水平(P<0.05,P<0.01),降低血清TBA水平,升高CYP7A1的表达水平(P<0.01),并逆转高脂饮食引起的BAs代谢紊乱,同时抑制肠道的TGR5和FXR1表达。[结论]五苓散能降低高脂饮食诱导的HLP小鼠血脂水平,该作用与上调CETP和PLTP的水平,促进胆固醇的逆转运及肝脏BAs代谢有关。
