Interference of protein tyrosine phosphatase non-receptor type 22 inhibits NLRP3 inflammasome activation to alleviate inflammation after cerebral hemorrhage in rats

WANG Lu; ZHANG Li; XIAO Han; GAN Hui; CHEN Hui

doi:10.16016/j.1000-5404.201907021

Di-san junyi daxue xuebao (Dec 2019)

Interference of protein tyrosine phosphatase non-receptor type 22 inhibits NLRP3 inflammasome activation to alleviate inflammation after cerebral hemorrhage in rats

WANG Lu,
ZHANG Li,
XIAO Han,
GAN Hui,
CHEN Hui

Affiliations

WANG Lu: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Key Laboratory of Child Development and Disorders Ministry of Education, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, 400016, China
ZHANG Li: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Key Laboratory of Child Development and Disorders Ministry of Education, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, 400016, China
XIAO Han: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Key Laboratory of Child Development and Disorders Ministry of Education, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, 400016, China
GAN Hui: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Key Laboratory of Child Development and Disorders Ministry of Education, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, 400016, China
CHEN Hui: Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Key Laboratory of Child Development and Disorders Ministry of Education, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, 400016, China

DOI: https://doi.org/10.16016/j.1000-5404.201907021
Journal volume & issue: Vol. 41, no. 24
pp. 2409 – 2416

Abstract

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Objective To investigate the role of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in inflammatory response following intracerebral hemorrhage (ICH) in rats and explore the mechanism that mediates its effect. Methods Rat models of ICH were established by injecting autologous blood into the brain of 30 SD rats, and Western blotting was performed at 3, 6, 12, 24, and 48 h after ICH (6 rats at each time point) and in 6 sham-operated rats to determine the time window of PTPN22 expression after ICH. Another 72 rats were randomized equally into sham operation group, ICH group, ICH+negative control (ICH+NC) group, and ICH+PTPN22 interference group, and the neurological function score (mNSS) and brain water content were assessed at 24 h after ICH or the sham operation. Western blotting was used to detect the expression of cleaved interleukin-18 (cleaved IL-18), cleaved-IL-1β and cleaved caspase-1 around the hematoma in the rats. Histomorphological changes of the brain tissues of the rats were observed using HE and Nissl staining, and the expression of myeloperoxidase (MPO) around the hematoma was detected using immunofluorescence staining. Results The expression of PTPN22 began to increase significantly at 12 h after ICH in the rats, peaked at 24 h and began to decrease at 48 h (P < 0.05). Compared with those in ICH+NC group, the rats in ICH+PTPN22 interference group had significantly lowered neurological scores and reduced brain water content (P < 0.05) with obviously alleviated brain tissue damage as shown by HE and Nissl staining. The expression of NLRP3, cleaved IL-1β, cleaved IL-18 and cleaved caspase-1 and the number of MPO-positive cells around the hematoma were all significantly lowered in PTPN22 interference group compared with ICH+NC group (P < 0.05). Conclusion Small interfering RNA-mediated interference of PTPN22 attenuates inflammatory response after ICH in rats by inhibiting the activation of NLRP3.

Published in Di-san junyi daxue xuebao

ISSN: 1000-5404 (Print)
Publisher: Editorial Office of Journal of Third Military Medical University
Country of publisher: China
LCC subjects: Medicine: Medicine (General)
Website: https://aammt.tmmu.edu.cn/

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