[1]曹木根,游濠乐,陈乐昀,等.晚期糖基化终产物通过TLR4/MD2通路介导心肌细胞炎症的机制研究[J].福建医药杂志,2024,46(07):64-68.[doi:10.20148/j.fmj.2024.07.021]
　CAO Mugen,YOU Haole,CHEN Leyun,et al.Study on mechanism of AGEs mediating inflammation of cardiomyocytes through TLR4/MD2 pathway[J].FUJIAN MEDICAL JOURNAL,2024,46(07):64-68.[doi:10.20148/j.fmj.2024.07.021]
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晚期糖基化终产物通过TLR4/MD2通路介导心肌细胞炎症的机制研究()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
46
期数:
2024年07期
页码:
64-68
栏目:
基础研究
出版日期:
2024-11-20

文章信息/Info

Title:
Study on mechanism of AGEs mediating inflammation of cardiomyocytes through TLR4/MD2 pathway
文章编号:
1002-2600(2024)07-0064-05
作者:
曹木根; 游濠乐; 陈乐昀; 魏潇琪; 郑炜平
福建医科大学省立临床医学院 福建省立医院老年科,福州 3500001
Author(s):
CAO Mugen;  YOU Haole;  CHEN Leyun;  WEI Xiaoqi;  ZHENG Weiping
Department of Geriatrics, 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;  晚期糖基化终末产物受体;  Toll样受体4;  髓样分化受体2
Keywords:
advanced glycation end products;  advanced glycation end product receptor;  toll-like receptor 4;  myeloid differentiation receptor 2
分类号:
R541
DOI:
10.20148/j.fmj.2024.07.021
文献标志码:
B
摘要:
目的 探讨晚期糖基化终产物(AGEs)通过Toll样受体4(TLR4)/髓样分化蛋白2(MD2)通路介导心肌细胞炎症的相关机制。方法 采用不同浓度的AGEs牛血清白蛋白(0、100、200、400、800 μg/mL)干预12、24、48、60、72 h,筛选最佳的AGEs干预H9c2细胞的浓度和干预时间。将细胞分成4个组别:对照组、AGEs组、MD2抑制剂组及AGEs+MD2抑制剂组。 采用CCK-8法检测各组细胞活力; 检测各组乳酸脱氢酶(LDH)含量; 采用ELISA法测定各组AGEs-MD2的浓度; 使用蛋白质印迹法检测各组心肌细胞中TLR4下游髓样分化因子88(MyD88)蛋白表达水平; Real time PCR法测定心肌细胞炎性相关指标白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)的mRNA表达水平。结果 与对照组相比,AGEs组的细胞存活率降低,LDH释放量升高,AGEs-MD2在450 nm处光密度增高,MyD88蛋白相对表达量增高,IL-6、TNF-α的mRNA相对表达量增高,差异有统计学意义(P<0.05); 与对照组相比, MD2抑制剂组细胞存活率降低,LDH释放量升高,差异有统计学意义(P<0.05)。与AGEs组相比,AGEs+MD2抑制剂组的AGEs-MD2在450 nm处光密度降低,MyD88蛋白相对表达量降低,IL-6、TNF-α的mRNA相对表达量降低,差异有统计学意义(P<0.05)。结论 AGEs可以通过TLR4/MD2通路激活MyD88下游的炎性因子介导心肌细胞炎症,这可能是体内AGEs长期积累引起心脏重构的机制之一。
Abstract:
Objective To explore the mechanisms by which advanced glycation end products(AGEs)mediate inflammation of cardiomyocytes through the toll-like receptor 4(TLR4)/ myeloid differentiation factor 2(MD2)pathway.Methods Intervention for 12, 24, 48, 60, 72 h was performed using different concentrations of AGEs bovine serum albumin(0, 100, 200, 400, 800 μg/mL)to identify the optimal AGEs concentration and intervention time.Subsequently, H9c2 cells were divided into four groups: control group, AGEs group, MD-2 inhibitor group, and AGEs + MD2 inhibitor group.The cell viability of H9c2 cells in each group was assessed using the CCK-8 assay.LDH levels in the culture medium of H9c2 cells were measured using a reagent kit.The concentrations of AGEs-MD2 in cardiomyocytes were measured by ELISA.The expression levels of MyD88 protein downstream of TLR4 in cardiomyocytes were detected by Western blot.The mRNA expression levels of IL-6 and TNF-α of inflammatory markers in cardiomyocytes were determined by real time PCR.Results Compared with the control group, the AGEs group showed a decrease in cell viability, an increase in LDH release, optical density at 450 nm for AGEs-MD2, relative protein expression of MyD88, and an increase in relative mRNA expression of IL-6 and TNF-α, and all the differences were statistically significant(P<0.05).Compared with the control group, the MD-2 inhibitor group showed a decrease in cell viability and an increase in LDH release,and all the differences were statistically significant(P<0.05).Compared with the AGEs group, the AGEs+MD2 inhibitor group showed a decrease in optical density at 450 nm for AGEs-MD2, a decrease in relative protein expression of MyD88, and a decrease in relative mRNA expression of IL-6 and TNF-α, and all the differences were statistically significant(P<0.05).Conclusion AGEs can activate cardimyocyte inflammation which is mediated by the inflammatory cytokines of MyD88 through the TLR4/MD2 pathway, which may be one of the mechanisms of cardiac remodeling caused by the long-term accumulation of AGEs in the body.

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相似文献/References:

[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.
　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(07):121.

备注/Memo

备注/Memo:
基金项目:福建省自然科学基金资助项目(2021J01401); 福建省卫生厅中青年骨干基金(2018-ZQN-10)
通信作者:郑炜平,Email:sycdxy66@163.com
更新日期/Last Update: 2024-11-20