[1]魏潇琪,王小易,林燕清,等.晚期糖基化终末产物与MD2-TLR4结合介导心脏衰老机制的研究[J].福建医药杂志,2021,43(01):121-124.
　WEI Xiaoqi,WANG Xiaoyi,LIN Yanqing,et al.Study on the mechanism of cardiac aging mediated by the combination of AGEs and MD2-TLR4[J].FUJIAN MEDICAL JOURNAL,2021,43(01):121-124.
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晚期糖基化终末产物与MD2-TLR4结合介导心脏衰老机制的研究()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
43
期数:
2021年01期
页码:
121-124
栏目:
基础研究
出版日期:
2021-02-10

文章信息/Info

Title:
Study on the mechanism of cardiac aging mediated by the combination of AGEs and MD2-TLR4
文章编号:
1002-2600(2021)01-0121-04
作者:
魏潇琪; 王小易; 林燕清; 陈志海; 游濠乐; 郑炜平1
福建医科大学省立临床医学院 福建省立医院老年科(福州 350001)
Author(s):
WEI Xiaoqi;  WANG Xiaoyi;  LIN Yanqing;  CHEN Zhihai;  YOU Haole; ZHENG Weiping.
Department of Geriatric Medicine,Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University,Fuzhou,Fujian 350001,China
关键词:
晚期糖基化代谢终末产物;  toll样受体4;  髓样分化受体2;  慢性心力衰竭
Keywords:
advanced glycosylation metabolic end products;  toll-like receptor 4;  myeloid differentiation receptor 2;  chronic heart failure
分类号:
R541.6
文献标志码:
A
摘要:
目的 探讨衰老过程中晚期糖基化终末产物(AGEs)是否能够通过髓样分化受体2(MD2)-toll样受体4(TLR4)途径介导慢性炎症,导致心肌重构、慢性心衰。方法 根据月龄,12只SD大鼠分成对照组(月龄3个月)与老年组(月龄24个月)各6只。对比两组心肌Masson染色结果,判断心肌排列情况及纤维化程度。对比二者心脏彩超结果,评价心功能变化。通过ELISA法检测,对比二者AGEs-MD2、IL-6、NT-pro-BNP表达差异。心肌组织行Western blot及RT-PCR检测,判断年轻组与老年组心肌MD2、TLR4及其下游信号表达情况。结果 老年组血清AGEs-MD2复合物在450 nm处吸光度较对照组增高(P<0.01)。血清IL-6和NT-pro-BNP表达较年轻组明显增高[(87.36±16.28)ng/L vs.(53.36±12.26)ng/L,P<0.01和(486.26±36.58)ng/L vs.(126.38±26.12)ng/L,P<0.01)]。心脏彩超结果显示老年组左心室舒张末期内径、左心室收缩末期内径较对照组升高,左室射血分数、E/A值下降。与对照组相比,老年组心肌细胞肥大、排列紊乱、过度纤维化。蛋白水平上,老年组心肌组织AGEs、MD2、TLR4表达较对照组明显增加(P<0.01)。mRNA水平上,老年组心肌组织TLR4的胞内衔接蛋白髓样分化因子88升高,心肌组织IL-6含量也增高(P<0.05)。结论 AGEs在心脏衰老过程中可在心肌组织中大量集聚,并通过AGEs-MD2-TLR4途径介导慢性炎症、心肌纤维化,导致心肌重构、慢性心衰。
Abstract:
Objective To investigate whether advanced glycation end products(AGEs)can mediate chronic inflammation, myocardial remodeling and chronic heart failure through myeloid differentiation 2(MD2)- toll like receptor 4(TLR4)pathway in the elderly.Methods According to the month of age, 12 SD rats were divided into control group(3 months old)and old group(24 months old)with 6 rats in each group.The results of Masson staining were compared between the two groups to observe the arrangement of myocardium and judge the degree of fibrosis.The echocardiography were performed to evaluate the changes of cardiac function.The ELISA method was employed to test serum AGEs-MD2 complex, IL-6 and NT-pro-BNP in rats.Western blot and RT-PCR were used to detect the expression of MD2, TLR4 and their downstream signals in young and old group.Results The absorbance of serum AGEs-MD2 complex at 450 nm in the elderly group was higher than that in the control group(P<0.01).The expression levels of IL-6 and NT-pro-BNP in serum were significantly higher than those in young group [(87.36±16.28)ng/L vs.(53.36±12.26)ng/L,P<0.01 and(486.26±36.58)ng/L vs.(126.38±26.12)ng/L,P<0.01)].The results of echocardiography showed that left ventricular end-diastolic dimension and left ventricular end-systolic dimension of the elderly group were higher than those of the control group, while the left ventricular ejection fraction and E/A value were lower.Compared with the control group, the myocardial cells in the elderly group were hypertrophic and disordered.There was much more myocardial fibrosis in the elderly group. Compared with the control group, the expression levels of TLR4 and MD2 were higher in the elderly group(P<0.01).At the mRNA level, the level of MyD88 and IL-6 in myocardial tissue were increased in the elderly group(P<0.05).Conclusion As hearts grow old, AGEs accumulate in myocardial tissue and form the AGEs-MD2-TLR4 complex which can mediate chronic inflammation and myocardial fibrosis, which may further cause myocardial remodeling and chronic heart failure.

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备注/Memo

备注/Memo:
基金项目:福建省自然科学基金资助项目(2018J01247); 福建省卫计委中青年骨干人才培养项目(2018-ZQN-10)
更新日期/Last Update: 2021-02-10