目的研究血浆和斑块局部受激活后调节性正常T细胞表达和分泌因子(regulated on activated normal T cellexpressed and secreted factor,RANTES)表达水平与兔动脉粥样硬化斑块内血管平滑肌细胞(vascular smooth musclecells,VSMCs)凋亡...目的研究血浆和斑块局部受激活后调节性正常T细胞表达和分泌因子(regulated on activated normal T cellexpressed and secreted factor,RANTES)表达水平与兔动脉粥样硬化斑块内血管平滑肌细胞(vascular smooth musclecells,VSMCs)凋亡程度的相关性。方法 40只雄性家兔随机分为:①空白组(Blank组)和②对照组(Control组):均普通饲料喂养;③稳定斑块组(AS组)和④易损斑块组(VAP组):均高脂饮食。Control和VAP组给予药物触发(蝰蛇毒+组织胺),Blank和AS组给予生理盐水。测定各组血脂和血浆RANTES水平,Real time-PCR和Western blot检测主动脉RANTES转录和表达水平,TUNEL染色后计算各组斑块血管平滑肌细胞(VSMCs)凋亡率及其与RANTES水平的相关系数。结果高脂喂养组家兔血脂水平较普通喂养组明显升高(P<0.01)。VAP组RANTES表达水平和凋亡率明显高于AS组(P<0.01)、Control组(P<0.01)和Blank组(P<0.01);AS组明显高于Control组(P<0.01)和Blank组(P<0.01);但Blank组和Control组间差异无统计学意义(P>0.05)。各组VSMCs凋亡率与RANTES表达水平均呈正相关(均P<0.05)。结论 RANTES过表达可能通过加重斑块局部的炎症反应而诱导斑块内VSMCs凋亡。展开更多
Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether n...Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.展开更多
文摘目的研究血浆和斑块局部受激活后调节性正常T细胞表达和分泌因子(regulated on activated normal T cellexpressed and secreted factor,RANTES)表达水平与兔动脉粥样硬化斑块内血管平滑肌细胞(vascular smooth musclecells,VSMCs)凋亡程度的相关性。方法 40只雄性家兔随机分为:①空白组(Blank组)和②对照组(Control组):均普通饲料喂养;③稳定斑块组(AS组)和④易损斑块组(VAP组):均高脂饮食。Control和VAP组给予药物触发(蝰蛇毒+组织胺),Blank和AS组给予生理盐水。测定各组血脂和血浆RANTES水平,Real time-PCR和Western blot检测主动脉RANTES转录和表达水平,TUNEL染色后计算各组斑块血管平滑肌细胞(VSMCs)凋亡率及其与RANTES水平的相关系数。结果高脂喂养组家兔血脂水平较普通喂养组明显升高(P<0.01)。VAP组RANTES表达水平和凋亡率明显高于AS组(P<0.01)、Control组(P<0.01)和Blank组(P<0.01);AS组明显高于Control组(P<0.01)和Blank组(P<0.01);但Blank组和Control组间差异无统计学意义(P>0.05)。各组VSMCs凋亡率与RANTES表达水平均呈正相关(均P<0.05)。结论 RANTES过表达可能通过加重斑块局部的炎症反应而诱导斑块内VSMCs凋亡。
文摘Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.
