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[1]魏瀟琪,王小易,林燕清,等.晚期糖基化終末產物與MD2-TLR4結合介導心臟衰老機制的研究[J].福建醫(yī)藥雜志,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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晚期糖基化終末產物與MD2-TLR4結合介導心臟衰老機制的研究()
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《福建醫(yī)藥雜志》[ISSN:1002-2600/CN:35-1071/R]

卷:
43
期數(shù):
2021年01期
頁碼:
121-124
欄目:
基礎研究
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
文章編號:
1002-2600(2021)01-0121-04
作者:
魏瀟琪王小易林燕清陳志海游濠樂鄭煒平1
福建醫(yī)科大學省立臨床醫(yī)學院 福建省立醫(yī)院老年科(福州 350001)
Author(s):
WEI Xiaoqi WANG Xiaoyi LIN Yanqing CHEN Zhihai YOU HaoleZHENG Weiping.
Department of Geriatric Medicine,Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University,Fuzhou,Fujian 350001,China
關鍵詞:
晚期糖基化代謝終末產物 toll樣受體4 髓樣分化受體2 慢性心力衰竭
Keywords:
advanced glycosylation metabolic end products toll-like receptor 4 myeloid differentiation receptor 2 chronic heart failure
分類號:
R541.6
文獻標志碼:
A
摘要:
目的 探討衰老過程中晚期糖基化終末產物(AGEs)是否能夠通過髓樣分化受體2(MD2)-toll樣受體4(TLR4)途徑介導慢性炎癥,導致心肌重構、慢性心衰。方法 根據(jù)月齡,12只SD大鼠分成對照組(月齡3個月)與老年組(月齡24個月)各6只。對比兩組心肌Masson染色結果,判斷心肌排列情況及纖維化程度。對比二者心臟彩超結果,評價心功能變化。通過ELISA法檢測,對比二者AGEs-MD2、IL-6、NT-pro-BNP表達差異。心肌組織行Western blot及RT-PCR檢測,判斷年輕組與老年組心肌MD2、TLR4及其下游信號表達情況。結果 老年組血清AGEs-MD2復合物在450 nm處吸光度較對照組增高(P<0.01)。血清IL-6和NT-pro-BNP表達較年輕組明顯增高[(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)]。心臟彩超結果顯示老年組左心室舒張末期內徑、左心室收縮末期內徑較對照組升高,左室射血分數(shù)、E/A值下降。與對照組相比,老年組心肌細胞肥大、排列紊亂、過度纖維化。蛋白水平上,老年組心肌組織AGEs、MD2、TLR4表達較對照組明顯增加(P<0.01)。mRNA水平上,老年組心肌組織TLR4的胞內銜接蛋白髓樣分化因子88升高,心肌組織IL-6含量也增高(P<0.05)。結論 AGEs在心臟衰老過程中可在心肌組織中大量集聚,并通過AGEs-MD2-TLR4途徑介導慢性炎癥、心肌纖維化,導致心肌重構、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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備注/Memo

備注/Memo:
基金項目:福建省自然科學基金資助項目(2018J01247); 福建省衛(wèi)計委中青年骨干人才培養(yǎng)項目(2018-ZQN-10)
更新日期/Last Update: 2021-02-10