مختصر البحث:
Ischemia reperfusion injury (IRI) is the net result of an inflammatory process which occurred when an organ suffered a transient decrease or cessation of the blood flow, followed by restoration
of perfusion. The kidney is considered as one of the m…
Ischemia reperfusion injury (IRI) is the net result of an inflammatory process which occurred when an organ suffered a transient decrease or cessation of the blood flow, followed by restoration
of perfusion. The kidney is considered as one of the most susceptible organs to IRI. IRI is considered one
of the major challenges of organ transplantation, because it directly correlates to the graft rejection. Oxidative stress is an important pathway that participates in the pathogenesis of IRI through enhancing of
ROS production. ROS react with cellular component leading to lipid peroxidation, inactivation of enzymes, oxidation of glutathione, formation of organic radical, and destruction of the cell. The inflammation and immune system play a serious function in the pathogenesis of renal IRI; renal IR upregulates the
gene expression of TLR in parts of kidney. Activation of these receptors leads to enhancement of inflammatory mediators which induce inflammatory responses, resulting in tubulointerstitial injury. Serelaxin
has anti-inflammatory, ant fibrotic, antihypertrophic, and cytoprotective effects. Serelaxin decrease infiltration of the inflammatory cells such as neutrophils, basophils, mast cells and macrophages to several injured or damaged tissues and decrease the cytokines and chemokine released by these cells. This research
aimed to investigate the renoprotective effect of serelaxinin on renal IRI in rat model by targeting TLR
signaling pathway. Twenty adult Sprague Dawley male rats were randomized into four equal groups:
sham group (underwent laparotomy but without IR, N = 5), control group (rats subjected to 30 min ischemia and 2 h reperfusion, N = 5), vehicle group (same as in control group + distilled water, N = 5), serelaxin group (as in control + 5 μg/kg SLX, N = 5). The kidney and blood were harvested after 2 h of reperfusion. Blood sample used to assessment SU and Scr. Kidney used to assessed tissue 8-iso PGF2α,
HMGB1, IL-1β, and TLR4 as well as the histological examination. Rats in control and vehicle groups observed a significant increase in SU, Scr, 8-iso PGF2α, IL-1β, HMGB1, and TLR4 comparing with sham
group. Histopathological study showed a significant elevation in injury score. Kidneys of serelaxin pretreated rats demonstrated histological and functional improvement as evidenced by significant decreased
in SU and Scr, and there were a significant diminishing in 8-iso PGF2α. HMGB, IL-1β, and TLR4 in pretreated group appeared significantly reduced compared with control and vehicle groups. Serelaxin diminished the kidney damage mediated by renal ischemia and reperfusion. This renoprotective effect may be
achieved by modulation of inflammatory response through inhibition of HMGB1-TLR4signaling pathway
and reduce its downstream IL-1β protein expression in addition to antioxidant effect.
