Citation: | LIU Xinyan, DONG Liyun, ZHOU Peipei, CHEN Yongxue, WANG Xinbo, SUN Yan. Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway[J]. Journal of Clinical Medicine in Practice, 2024, 28(15): 19-25. DOI: 10.7619/jcmp.20240407 |
To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway.
Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group.
Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (P < 0.05). The serum levels of CK-MB, cTnI, LDH, TNF-α, IL-6, IL-1β, myocardial injury and apoptosis, caspase 1/3/9 protein levels in myocardial tissue sections, neutrophil counts, and GSK-3β and NLRP3 protein levels were significantly increased in the model group, and these indicators were significantly lower in the esketamine group than in the model group (P < 0.05).
Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by inhibiting inflammation, and its mechanism of action is related to the GSK-3β/NLRP3 pathway.
[1] |
BOBBA P S, MALHOTRA A, SHETH K N, et al. Brain injury patterns in hypoxic ischemic encephalopathy of term neonates[J]. J Neuroimaging, 2023, 33(1): 79-84. doi: 10.1111/jon.13052
|
[2] |
XU Y H, XU J B, CHEN L L, et al. Protective mechanisms of quercetin in neonatal rat brain injury induced by hypoxic-ischemic brain damage (HIBD)[J]. Food Sci Nutr, 2023, 11(12): 7649-7663. doi: 10.1002/fsn3.3684
|
[3] |
MANABE M, FUJINO M, KUSUKI H, et al. Effect of hypothermia on myocardial depolarization and repolarization in neonates with hypoxic-ischemic encephalopathy due to asphyxia[J]. Pediatr Cardiol, 2022, 43(8): 1792-1798. doi: 10.1007/s00246-022-02916-x
|
[4] |
SODA T, BRUNETTI V, BERRA-ROMANI R, et al. The emerging role of N-methyl-D-aspartate (NMDA) receptors in the cardiovascular system: physiological implications, pathological consequences, and therapeutic perspectives[J]. Int J Mol Sci, 2023, 24(4): 3914. doi: 10.3390/ijms24043914
|
[5] |
李芷宜, 杨秀娟. 艾司氯胺酮药物研究进展[J]. 山西化工, 2022, 42(4): 21-23, 26. https://www.cnki.com.cn/Article/CJFDTOTAL-SDHW202204008.htm
|
[6] |
杨鑫, 朱免免, 胡利, 等. 艾司氯胺酮预处理联合低CO2气腹压对腔镜疝气手术患儿术中神经、呼吸系统的保护作用研究[J]. 临床和实验医学杂志, 2022, 21(11): 1230-1233. https://www.cnki.com.cn/Article/CJFDTOTAL-SYLC202211030.htm
|
[7] |
LIAN X H, LIN Y Z, LUO T, et al. Efficacy and safety of esketamine for sedation among patients undergoinggastrointestinal endoscopy: a systematic review and meta-analysis[J]. BMC Anesthesiol, 2023, 23(1): 204. doi: 10.1186/s12871-023-02167-0
|
[8] |
DAI J W, LI S L, ZHENG R Y, et al. Effect of esketamine on inflammatory factors in opioid-free anesthesia based on quadratus lumborum block: a randomized trial[J]. Medicine, 2023, 102(37): e34975. doi: 10.1097/MD.0000000000034975
|
[9] |
ZHOU S, LIU Y, XUE B B, et al. Low-dose Esketamine suppresses NLRP3-mediated apoptotic and pyroptotic cell death in microglial cells to ameliorate LPS-induced depression via ablating GSK-3β[J]. Behav Brain Res, 2024, 459: 114782. doi: 10.1016/j.bbr.2023.114782
|
[10] |
KAWAKAMI M D, SANUDO A, TEIXEIRA M L P, et al. Neonatal mortality associated with perinatal asphyxia: a population-based study in a middle-income country[J]. BMC Pregnancy Childbirth, 2021, 21(1): 169. doi: 10.1186/s12884-021-03652-5
|
[11] |
OKAZAKI K, NAKAMURA S, KOYANO K, et al. Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines[J]. Front Pediatr, 2023, 11: 1070743. doi: 10.3389/fped.2023.1070743
|
[12] |
袁培根, 杨晓丹, 单鸳露, 等. 低剂量艾司氯胺酮通过TLR4/MyD88/NF-κB通路减轻肢体缺血再灌注损伤[J]. 中国现代医生, 2023, 61(31): 82-85, 89. https://www.cnki.com.cn/Article/CJFDTOTAL-ZDYS202331018.htm
|
[13] |
LI Y L, GEERTMAN S, HOOIMEIJER P, et al. Do migrants and locals differ in commuting behavior?A case study of Xiamen, China[J]. Transp Policy, 2021, 108: 1-10. doi: 10.1016/j.tranpol.2021.04.020
|
[14] |
ZAMAN G S, MIR M A, BASHIR N, et al. Comparison of creatine kinase-MB, troponin-I, troponin-T, triiodothyronine, thyroxine, apoprotein-B and homocysteine between non-smokers, smokers at high altitudes, and smokers at sea level[J]. Cell Mol Biol, 2023, 69(2): 101-109. doi: 10.14715/cmb/2023.69.2.17
|
[15] |
ABDOLSAMAD H I A, TEHRANIPOUR M, MAHMODZADEH A H, et al. Effect of aqueous and alcoholic extracts of Ziziphora clinopodioides on apoptosis and alteration of caspase-3 and caspase-9 gene expression in anterior horn neurons of the spinal cord after sciatic nerve compression in male rats[J]. J Birjand Univ Med Sci, 2021: 222-235. doi: 10.32592/JBirjandUnivMedSci.2021.28.3.101
|
[16] |
ZHANG J, ZHENG X X, WANG P Y, et al. Role of apoptosis repressor with caspase recruitment domain (ARC) in cell death and cardiovascular disease[J]. Apoptosis, 2021, 26(1/2): 24-37.
|
[17] |
CHEN Y M, HE Y C, ZHAO S C, et al. Hypoxic/ischemic inflammation, microRNAs and δ-opioid receptors: hypoxia/ischemia-sensitive versus-insensitive organs[J]. Front Aging Neurosci, 2022, 14: 847374. doi: 10.3389/fnagi.2022.847374
|
[18] |
CLAUZURE M, VALDIVIESO Á G, DUGOUR A V, et al. NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) modulation by intracellular Cl- concentration[J]. Immunology, 2021, 163(4): 493-511. doi: 10.1111/imm.13336
|
[19] |
YANG Y, LIU P Y, BAO W, et al. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway[J]. BMC Cancer, 2020, 20(1): 28. doi: 10.1186/s12885-019-6491-6
|
[20] |
张丹眉, 石春霞, 龚作炯. 糖原合酶激酶3β抑制剂TDZD-8对急性肝细胞损伤中自噬及NLRP3炎性小体的影响[J]. 医学研究杂志, 2023, 52(10): 31-36. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYZ202310026.htm
|