[1]张炜 杨海龙 谢润阳.Kiss-10通过调控GPR54/NF-κB通路改善尿毒症毒素吲哚-3-乙酸诱导的心肌损伤[J].心血管病学进展,2025,(2):179.[doi:10.16806/j.cnki.issn.1004-3934.2025.02.017]
　ZHANG Wei,YANG Hailong,XIE Runyang.Kisspeptin-10 Ameliorates Myocardial Damage Induced by Uremic Toxin Indole-3-Acetic Acid by Regulating the GPR54/NF-B Pathway[J].Advances in Cardiovascular Diseases,2025,(2):179.[doi:10.16806/j.cnki.issn.1004-3934.2025.02.017]
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Kiss-10通过调控GPR54/NF-κB通路改善尿毒症毒素吲哚-3-乙酸诱导的心肌损伤()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年2期
页码:
179
栏目:
论著
出版日期:
2025-02-25

文章信息/Info

Title:
Kisspeptin-10 Ameliorates Myocardial Damage Induced by Uremic Toxin Indole-3-Acetic Acid by Regulating the GPR54/NF-B Pathway
作者:
张炜1 杨海龙1 谢润阳2
宝鸡高新医院心血管内科,陕西 宝鸡 721000;2. 宝鸡高新医院介入血管科,陕西 宝鸡 721000)
Author(s):
ZHANG Wei1; YANG Hailong1; XIE Runyang 2
(1. Cardiovascular Department,Baoji High tech Hospital,Baoji 721000,Shaanxi,China2. Interventional Vascular Department,Baoji High tech Hospital,Baoji 721000Shaanxi,China)
关键词:
吲哚- 3-乙酸; 心肌损伤; 亲吻促动素-10; GPR54/NF-κB通路; 炎症反应
Keywords:
Indole-3-acetic acid; Myocardial injury; Kisspeptin-10; GPR54/NF-B pathway; Inflammatory reaction
DOI:
10.16806/j.cnki.issn.1004-3934.2025.02.017
摘要:
目的 探究亲吻促动素-10（Kiss-10）通过调控G蛋白偶联受体54（GPR54）/核因子-κB（NF-κB）通路对尿毒症毒素吲哚-3-乙酸（IAA）诱导的心肌损伤的影响机制。方法 培养心肌细胞H9c2，利用CCK-8试剂盒检测心肌细胞活性筛选IAA与Kiss-10干预浓度，分组为对照组、IAA组与Kiss-10组。将30只小鼠分为如上所述3组，每组10只。免疫荧光染色检测心肌细胞大小。RT-qPCR检测心房利钠肽（ANP）、脑钠肽（BNP）与心肌肌球蛋白重链β（β-MHC）的mRNA水平。Western blotting检测GPR54与NF-κB蛋白水平。ELISA试剂盒检测白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）含量。苏木精-伊红（HE）染色检测心肌组织病理变化。超声心动图检测左心室后壁收缩末期厚度（LVPWs），左心室后壁舒张末期厚度?（LVPWd），左心室前壁收缩期厚度（LVAWs），左心室前壁舒张期厚度（LVAWd）及E/A。结果 使用不同浓度IAA（5、10、30、50、100 μmol/L）处理心肌细胞24 h，随着IAA浓度的增加，心肌细胞活性逐渐降低（P<0.05，P<0.01），其中50 μmol/L约为半数细胞活性抑制浓度，因此选该浓度继续后续实验。不同浓度Kiss-10（5、10、20 μmol/L）对心肌细胞活性无显著性影响（P>0.05）。对照组相比，IAA组心肌细胞活性降低（P<0.05），心肌细胞形态变大，ANP、BNP与β-MHC的mRNA水平增加（P<0.05），心肌细胞与心肌组织中GPR54表达减少，NF-κB表达增加（P<0.05），细胞上清液与血清中IL-1β、IL-6、TNF-α含量增加（P<0.05），小鼠心肌明显肥厚，LVPWs、LVPWd、LVAWs及LVAWd增加，E/A降低（P<0.05）；与IAA组相比，Kiss-10组心肌细胞活性随Kiss-10浓度增加而逐渐增加（P<0.05），后期选择20 μmol/L的Kiss-10进行研究，Kiss-10组心肌细胞形态结构变小，ANP、BNP与β-MHC的mRNA水平减少（P<0.05），心肌细胞与心肌组织中GPR54表达增加，NF-κB表达减少（P<0.05），细胞上清液与血清中IL-1β、IL-6、TNF-α含量减少（P<0.05），小鼠心肌肥厚程度降低，LVPWs、LVPWd、LVAWs及LVAWd减少，E/A增加（P<0.05）。结论 Kiss-10通过调控GPR54/NF-κB通路改善IAA诱导的心肌功能结构及炎性损伤。
Abstract:
Objective To investigate the effect of kisspeptin-10 (Kiss-10) on myocardial injury induced by uremic toxin indole-3-acetic acid (IAA) through regulating G protein-coupled receptor 54 (GPR54)/nuclear factor-κB (NF-κB) pathway. Methods H9c2 cells were cultured, and CCK-8 kit was used to detect the activity of cardiomyocytes to screen the intervention concentrations of IAA and Kiss-10. Thirty mice were divided into 3 groups as described above, with 10 mice in each group. The size of cardiomyocytes was detected by immunofluorescence staining. The mRNA levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cardiac myosin heavy chain β (β-MHC) were detected by RT-qPCR. Western blotting was used to detect the protein levels of GPR54 and NF-κB. The levels of interleukin(IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were detected by ELISA kits. hematoxylin and eosin staining was used to detect the pathological changes of myocardial tissue. Left ventricular posterior wall end-systolic thickness (LVPWs), left ventricular posterior wall end-diastolic thickness ? (LVPWd), left ventricular anterior wall end-systolic thickness (LVAWs), left ventricular anterior wall end-diastolic thickness (LVAWd) and E/A ratio were measured by echocardiography. Results Different concentrations of IAA (5, 10, 30, 50, and 100 μmol/L) were used to treat cardiomyocytes for 24 h. With the increase of IAA concentration, the viability of cardiomyocytes was gradually decreased (P<0.05, P<0.01), and 50 μmol/L was about the 50% inhibitory concentration of cell viability, so this concentration was selected for subsequent experiments. Different concentrations of Kiss-10 (5, 10, 20 μmol/L) had no significant effect on the viability of cardiomyocytes (P>0.05). Compared with the control group, the activity of cardiomyocytes was decreased (P<0.05), the morphology of cardiomyocytes was enlarged, the mRNA levels of ANP, BNP and β-MHC were increased (P<0.05), the expression of GPR54 in cardiomyocytes and myocardial tissue was decreased, and the expression of NF-κB was increased in IAA group (P<0.05). The contents of IL-1β, IL-6 and TNF-α in the cell supernatant and serum were increased (P<0.05). The mice showed obvious myocardial hypertrophy, LVPWs, LVPWd, LVAWs and LVAWd were increased, and E/A was decreased (P<0.05). Compared with IAA group, the viability of cardiomyocytes in Kiss-10 group increased gradually with the increase of Kiss-10 concentration (P<0.05). The morphological structure of cardiomyocytes in Kiss-10 group became smaller, and the mRNA levels of ANP, BNP and β-MHC decreased (P<0.05). The expression of GPR54 in cardiomyocytes and myocardial tissue was increased, while the expression of NF-κB was decreased (P<0.05). The contents of IL-1β, IL-6 and TNF-α in cell supernatant and serum were decreased (P<0.05). E/A ratio increased (P<0.05). Conclusion Kiss-10 can improve IAA-induced myocardial functional structure and inflammatory damage by regulating GPR54/NF-κB pa thway

参考文献/References:

[1].Lim YJ,Sidor NA,Tonial NC,et al. Uremic toxins in the progression of chronic kidney disease and cardiovascular disease:Mechanisms and Therapeutic Targets[J]. Toxins (Basel),2021,13(2):142.
[2].Cernaro V,Calabrese V,Loddo S,et al. Indole-3-acetic acid correlates with monocyte-to-high-density lipoprotein (HDL) ratio (MHR) in chronic kidney disease patients[J]. Int Urol Nephrol,2022,54(9):2355-2364.
[3].Nayak SPRR,Boopathi S,Chandrasekar M,et al. Indole-3 acetic acid induced cardiac hypertrophy in wistar albino rats[J]. Toxicol Appl Pharmacol,2024,486:116917.
[4].Cao Y,Hu G,Zhang Q,et al. Kisspeptin-10 maintains the activation of the mTOR signaling pathway by inhibiting SIRT6 to promote the synthesis of milk in bovine mammary epithelial cells[J]. J Agric Food Chem,2021,69(14):4093-4100.
[5].Son HE,Kim KM,Kim EJ,et al. Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation[J]. Sci Rep,2018,8(1):2134.
[6].Qin YS,Bai JH,Zhang SL,et al. Effects of kisspeptin-10 on the reproductive performance of sows in a fixed-time artificial insemination programme[J]. Animal,2022,16(5):100509.
[7].Watanabe T,Sato K. Roles of the kisspeptin/GPR54 system in pathomechanisms of atherosclerosis[J]. Nutr Metab Cardiovasc Dis,2020,30(6):889-895.
[8].Dinh H,Kovács ZZA,Kis M,et al. Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy[J]. Geroscience,2024,46(2):2463-2488.
[9].Wang D,Wu Z,Zhao C,et al. KP-10/Gpr54 attenuates rheumatic arthritis through inactivating NF-κB and MAPK signaling in macrophages[J]. Pharmacol Res,2021,171:105496.
[10].GBD Chronic Kidney Disease Collaboration. Global,regional,and national burden of chronic kidney disease,1990-2017:a systematic analysis for the global burden of disease study 2017[J]. Lancet,2020,395(10225):709-733.
[11].Han X,Zhang S,Chen Z,et al. Cardiac biomarkers of heart failure in chronic kidney disease[J]. Clin Chim Acta,2020,510:298-310.
[12].Velasquez MT,Centron P,Barrows I,et al. Gut microbiota and cardiovascular uremic toxicities[J]. Toxins (Basel),2018,10(7):287.
[13].Li D,Guo YY,Cen XF,et al. Lupeol protects against cardiac hypertrophy via TLR4-PI3K-Akt-NF-κB pathways[J]. Acta Pharmacol Sin,2022,43(8):1989-2002.
[14].Zhang Y,Hou Y,Wang X,et al. The effects of kisspeptin-10 on serum metabolism and myocardium in rats[J]. PLoS One,2017,12(7):e0179164.
[15].Radwańska P,Ga?dyszyńska M,Piera L,et al. Kisspeptin-10 increases collagen content in the myocardium by focal adhesion kinase activity[J]. Sci Rep,2023,13(1):19977.
[16].Zhang S,Yu F,Che A,et al. Neuroendocrine regulation of stress-induced T cell dysfunction during lung cancer immunosurveillance via the Kisspeptin/GPR54 signaling pathway[J]. Adv Sci (Weinh),2022,9(13):e2104132.
[17].Zhu N,Zhao M,Song Y,et al. The KiSS-1/GPR54 system:Essential roles in physiological homeostasis and cancer biology[J]. Genes Dis,2020,9(1):28-40.

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更新日期/Last Update: 2025-03-11