Preactivated and disaggregated shape-changed platelets protect kidney against from ischemia-reperfusion injury in rat through attenuating inflammation reaction

This study tested the hypothesis that preactivated and disaggregated shape-changed platelet (PreD-SCP) therapy significantly protected rat kidney from ischemia-reperfusion (IR) injury. Adult-male Sprague-Dawley rats (n = 24) were equally categorized into Groups 1 (sham-operated control [SC]), 2 (SC + PreD-SCP), 3 (IR only), and 4 (IR + PreD-SCP). By 72 hr after IR procedure, the circulatory levels of creatinine, blood urine nitrogen and inflammatory biomarkers (interleukin [IL]-6/tumor necrosis factor [TNF]-alpha), and ratio of urine protein to urine creatinine were significantly higher in Group 3 than in other groups and significantly higher in Group 4 than in Groups 1 and 2, but they showed no different between Groups 1 and 2 (all p <.001). The microscopic findings showed that the expressions of kidney injury score, cellular inflammation (MMP-9/CD14//F4/80), and fibrotic area were identical to the circulatory inflammation, whereas the integrity of podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite to circulatory inflammation among the four groups (all p < .0001). The protein expressions of inflammatory (TNF-alpha/IL-1 beta/NF-kappa B/iNOS/TRAF6/MyD88/TLR-4), apoptotic/cell death (mitochondrial Bax/cleaved caspase-3/p-53), oxidized protein, mitogen-activated protein kinase family (p-38/p-JNK/p-c-JUN), and mitochondrial-damaged biomarkers displayed a similar pattern, whereas the antiapoptotic (Bcl-2/Bcl-XL) and integrity of mitochondrial biomarkers followed an opposite trend to circulatory inflammation among the four groups (all p < .001). PreD-SCP therapy effectively protected the kidney against IR injury.