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The potential role of CpG oligodeoxynucleotides on diabetic cardiac autonomic neuropathy mediated by P2Y12 receptor in rat stellate ganglia.
Li, Lin; Du, Junpei; Liu, Shipan; Yang, Runan; Xu, Xiumei; Yang, Yuxin; Ma, Xiaoqian; Li, Guilin; Liu, Shuangmei; Li, Guodong; Liang, Shangdong.
Affiliation
  • Li L; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Du J; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Liu S; Undergraduate Student at Class 2103, First Clinical Medical College of Nanchang University, Nanchang 330006, PR China.
  • Yang R; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Xu X; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Yang Y; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Ma X; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Li G; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Liu S; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Li G; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China.
  • Liang S; Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, PR China; Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, PR China. Electronic address: liangsd@hotmail.com.
Int Immunopharmacol ; 119: 110044, 2023 Jun.
Article in En | MEDLINE | ID: mdl-37264553
Cardiac autonomic neuropathy has a high prevalence in type 2 diabetes, which increases the risk of cardiovascular system disorders. CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to have cardioprotection and cellular protection. Our previous work showed that P2Y12 in stellate ganglia (SG) is involved in the process of diabetic cardiac autonomic neuropathy (DCAN). Here, we aim to investigate whether CpG-ODN 1826 plays a protective role in DCAN and whether this beneficial protection involves regulation of the P2Y12-mediated cardiac sympathetic injury. Our results revealed that CpG-ODN 1826 activated TLR9 receptor, improved the abnormal blood pressure (BP), heart rate (HR), heart rate variability (HRV) and sympathetic nerve discharge (SND) activity in diabetic rats and reduced the up-regulated NF-κB, P2Y12 receptor, TNF-α and IL-1ß in SG. Meanwhile, CpG-ODN 1826 significantly decreased the elevated ATP, nuclear receptor coactivator 4 (NCOA4), iron, ROS and MDA levels and increased GPX4 and GSH levels. In addition, CpG-ODN 1826 contributes to maintain normalization of mitochondrial structure in SG. Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Int Immunopharmacol Journal subject: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Year: 2023 Document type: Article Country of publication: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Int Immunopharmacol Journal subject: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Year: 2023 Document type: Article Country of publication: Netherlands