The Protective Effect of Tanshinone ⅡA on Oxygen-glucose Deprivation and Reperfusion Injury of MicrogliaThrough the NLRP3 Inflammatory Signaling Pathway

CAI Lin, YI Xiao-bo, YUAN Li-bang. et al

Abstract

To investigate the protective effect of Tanshinone ⅡA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. Methods The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 μg/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA. In TSA 0 (also called OGD group), 0.5, 1.0, 2.0 μg/mL groups, expression levels of NLRP3 and caspase-1 were detected by Western blot, while IL-1β and IL-18 in culture medium of those groups were detected by ELISA assay. Results The highest expression level of NLRP3 came to 12 h of reperfusion. The maximum effective concentration of TSA was 2.0 μg/mL. The expression levels of NLRP3, caspase-1, IL-1β and IL-18 decreased with the increase of TSA concentration. Conclusion TSA can inhibit the expression of protein and cytokines of NLRP3 inflammatory signaling pathway in OGD/R BV-2 cells, which may be one of the molecular mechanisms of the protective effect of TSA on OGD/R cells.

 

Keywords: Cerebral ischemia, Tanshinone ⅡA, Oxygen-glucose deprivation and reperfusion 

 

Full Text:

PDF


References


RAJAMAKI К, LAPPALAINEN J, OORNI K, et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel Link between cholesterol metabolism ami inflammation. PLoS One. 2010,5 (7): el 1765 Г2016-01-17]. http://www. ncbi. nlm. nih. gov/pmc/articles/ PMC2909263/pdf/pone.0011765. pdf. doi: 10. 1371/journal, pone. 0011765.

DK NARNO D, DE NARNO CM, LATZ E. New insights into mechanisms controlling the NLRP3 inflammasome and its role in lung disease. Am J Pathol,2014.184(1) ;42-54. TAN MS, YU JT, JIANG T, et al. The NLRP3 inflammasome in Alzheimer’s disease. Mol Neurobiol, 2013, 48(3) =875-882.

YANG F, WANG Z, WEI X, et al. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab.2014 ,34(4) : 660-667.

WU WY, WANG WY, MA YL, et al. Sodium tanshinone II A silate inhibits oxygen-glucose deprivation/recovery- induced cardiomyocyte apoptosis via suppression of the NF- кВ/TNF-a pathway. Br J Pharmacol, 2013, 169 ( 5 ): 1058- 1071.

PENDLEBURY ST, ROTH WELL PM. Prevalence, incidence andfactorsassociated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol.2009,8(11): 1006-1018.

WAT AN A BET, YU КI S. EGAWA M. et al. Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. J Pharmacol Exp Ther, 1994,268(3): 1597-1604.

FANN DY, LEE SY, MANZANERO S, et al. Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Disease. 2013. 4 (9): e790[2016-04-26]. http:// www. ncbi. nlm.nih.gov/pmc/articles/PMC3789184/pdf/cddis. 2013. 326. pdf. doi: 10.1038/journal, cddis. 2013. 326.

MCGETTRICK AF, O’NEILL LA. NLRP3 and IL-lp in macrophages as critical regulators of metabolic diseases. Diabetes Obes Metab,2013,15(Suppl 3): 19-25.

MARTINON F. Detection of immune danger signals by NALP3. Leu кос Biolb. 2008.83(3) :507-511.

CHEN Y. WU X. YU S. et al. Neuroprotection of tanshinone II A against cerebral ischemia/reperfusion injury through inhibition of macrophage migration inhibitory factor in rats. PLoS One,2012,7(6) :e40165[2016-01-28]. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3387137/pdf/ pone. 0040165. pdf. doi:10.1371/journal, pone. 0040165.

SMITH NM, GACHUUNCOVA I, HO D, et al. An unexpected transient breakdown of the blood brain barrier triggers passage of large intravenously administered nanoparticles. Sci Rep.201f>(6):22595[2016-03-04]. http:// www. nature, com/articles/srep 22595. doi: 10. 1038/srep22595.

ECHEVERRY S. SHI XQ. RIVEST S. et al. Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J Neurosci.2011 ,31(30): 10819-10828.

VILLACAMPA N. ALMOLDA B. V1LKLLA A, et al. Astrocyte-targeted production of IL-10 induces changes in microglial reactivity and reduces motor neuron death after facial nerve axotomy. (ilia.2015,63С7): 1166-1184.

CHABOTS. YONG VW. Interferon beta-lb increases interleukin-10 in a model of T cell-microglia interaction: relevance to MS. Neurology.2000,55( 10): 1497-1505.


Refbacks

  • There are currently no refbacks.