Effects of NLRP6 in Cerebral Ischemia/Reperfusion (I/R) Injury in Rats

• Published in: Journal of molecular neuroscience 2019-11, Vol.69 (3), p.411-418
• Main Authors: Meng, Changchang, Zhang, Jinyan, Zhang, Luyu, Wang, Yueting, Li, Zhenyu, Zhao, Jing
• Format: Article
• Language: English
• Subjects: Animals; Binding; Biomedical and Life Sciences; Biomedicine; Brain; Brain - pathology; Brain Edema - etiology; Brain Edema - prevention & control; Brain injury; Caspase; Caspase 1 - metabolism; Caspase-1; Cell Biology; Cerebral blood flow; Enzyme-linked immunosorbent assay; Gene expression; Gene Expression Regulation; IL-1β; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Inflammation; Injury prevention; Interleukin 18; Interleukin-18 - biosynthesis; Interleukin-1beta - biosynthesis; Ischemia; Leucine; Male; mRNA; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurochemistry; Neurology; Neurosciences; Nucleotides; Occlusion; Pattern recognition; Pattern recognition receptors; Peroxidase; Proteins; Proteomics; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin - genetics; Receptors, Angiotensin - physiology; Receptors, Vasopressin - genetics; Receptors, Vasopressin - physiology; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA Interference; RNA, Messenger - biosynthesis; RNA, Small Interfering - pharmacology; RNA, Small Interfering - therapeutic use; Single-Blind Method; siRNA
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-019-01370-4

The NOD-like receptor protein 6 (NLRP6), an intracytoplasmic pattern recognition receptor in the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, influences the inflammation reaction. The role of NLRP6 in cerebral ischemia-reperfusion (I/R) injury in rats is unclear. We explore the function of NLRP6 in cerebral I/R injury. The investigators used a middle cerebral artery occlusion/reperfusion model (MCAO) to imitate ischemic injury. We found the peak expression of NLRP6 is in 48-h post-cerebral I/R injury. The expression of NLRP6 siRNA, as well as the expression of protein and mRNA, was detected by Western blot and qRT-PCR. The degree of IL-1β and IL-18 was assessed by ELISA. After downregulating NLRP6, the expression of IL-1β, IL-18, cleaved Caspase-1, and myeloperoxidase (MPO) were reduced. In HE and Nissl staining, pathological injury of brain tissue after downregulating NLRP6 was improved. NLRP6 siRNA decreased the NLRP6-ASC binding states by CO-IP. NRP6 has a pro-inflammatory effect in cerebral I/R injury, which may provide a new target for the treatment of cerebral I/R injury.