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国家自然科学基金(81100857)

作品数:4 被引量:22H指数:2
相关作者:李晓宇李楠何龙杨清单清更多>>
相关机构:南京医科大学扬州市第一人民医院更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划南京医科大学科技发展基金更多>>
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脂多糖上调小鼠肝脏PCSK9升高血浆低密度脂蛋白胆固醇被引量:2
2011年
目的:研究感染和炎症时前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)在调节血浆低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)代谢中的作用及其可能的分子机制。方法:用全自动生化仪监测小鼠血浆总胆固醇、高密度脂蛋白胆固醇、甘油三酯、磷脂以及谷氨酸氨基转移酶含量。同时,用快速液相色谱(fast proteinliquid chromatography,FPLC)分析混合的小鼠血浆。血浆淀粉样蛋白A(serum amyloid A,SAA)浓度用酶联免疫吸附法测定。用定量PCR法检测肝脏组织的PCSK9、LDL受体等脂代谢相关基因mRNA丰度,并用Western blot分析肝组织中LDL受体表达变化。结果:研究发现低剂量脂多糖(liposacaridica,LPS)注射24 h后血浆谷氨酸氨基转移酶无明显变化,小鼠血浆LDL-C增高43.02%,高密度脂蛋白胆固醇增高30.09%、甘油三酯增高27.21%,磷脂增高25.50%。LPS注射组动物的血浆SAA明显增多至(1 271.05±94.13)ng/ml,增多的SAA主要与高密度脂蛋白和低密度脂蛋白结合。LPS处理诱导肝脏PCSK9基因表达上调,抑制肝脏LDL受体的蛋白表达。结论:研究表明LPS引起肝细胞中PCSK9上调,LDL受体蛋白表达受抑制,同时小鼠血浆LDL-C迅速增多,提示PCSK9抑制LDL受体通路可能通过影响血浆脂蛋白代谢在炎症导致的宿主反应中起重要作用。
李晓宇单清李楠杨清何龙
关键词:PCSK9低密度脂蛋白胆固醇
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage被引量:9
2014年
Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization.Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for cell survival under endoplasmic reticulum(ER) stress.We previously found that the engagement of class A scavenger receptor(SR-A) triggered JNK-dependent apoptosis in ER-stressed macrophages.However,pro-apoptotic mechanisms mediated by SR-A are not fully understood.Therefore,we sought to see if SR-A mediated apoptosis was associated with autophagy in macrophages.Here,we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates(LC3-Ⅱ) formation as well as the number of autophagosomes under ER stress.The inhibition of LC3-Ⅱ formation was paralleled by the activation of the mTOR pathway,and the inhibition of mTOR allowed LC3-Ⅱ induction in macrophages treated with thapsigargin plus fucoidan.Furthermore,apoptosis induced by fucoidan was prevented under ER stress by the mTOR inhibitor.We propose that fucoidan,a SR-A agonist,may contribute to macrophage apoptosis during ER stress by inhibiting autophagy.
Hanpeng HuangXiaoyu LiYan ZhuangNan LiXudong ZhuJin HuJingjing BenQing YangHui BaiQi Chen
关键词:SR-AAUTOPHAGYAPOPTOSISMACROPHAGE
Glycine attenuates myocardial ischemia-reperfusion injury by inhibiting myocardial apoptosis in rats被引量:10
2012年
Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we found that glycine reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with that in the vehicle-treated MI/R rats.The left ventricular ejection fraction and fractional shortening were increased by 19.11% and 30.98%,respectively,in glycine-treated rats.The plasma creatine kinase levels in ischemia-reperfusion injury rats decreased following glycine treatment.Importantly,administration of glycine significantly inhibited apoptosis in post-ischemia-reperfusion myocardium,which was accompanied by suppression of phosphorylated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase,as well as the Fas ligand.These results suggest that gly-cine attenuates myocardial ischemia-reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.
Xiaozheng ZhongXiaoyu LiLingling QianaYiming XuYan LuJing ZhangNan LiXudong ZhuJingjing BenQing YangQi Chen
关键词:GLYCINEAPOPTOSISCARDIOMYOCYTES
激光多普勒血流仪监测C57BL/6小鼠永久性大脑中动脉闭塞模型被引量:1
2014年
目的评估激光多普勒血流仪监测C57BL/6小鼠永久性大脑中动脉闭塞(MCAO)模型的可行性。方法 C57BL/6小鼠随机分为2组,假手术组和永久性MCAO组。线栓法制作永久性大脑中动脉闭塞模型,激光多普勒仪实时监测小鼠脑血流,术后神经功能学评分,24 h后2,3,5-三苯基氯化四氮唑染色确定梗死体积。结果 MCAO组术前脑血流(186.78±62.50)PU,栓线插入成功后患侧脑血流降低到(25.80±7.66)PU,降低了90.4%。神经功能学评分在(2.48±0.36)分,脑梗死面积达39.79%。假手术组脑血流在基础值波动,未见降低;神经功能学评分为0分,未见脑梗死病灶。结论激光多普勒血流仪监测是一个很好的确定小鼠脑梗死模型成功与否的筛选方法。
杨青徐益鸣李晓宇
关键词:激光多普勒血流仪C57BL
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