Ischemic postconditioning ameliorates acute kidney injury induced by limb ischemia/reperfusion via transforming TLR4 and NF-κB signaling in rats

Abstract

Background The present study investigated the influence of ischemic postconditioning (I-postC) on the adjustment of renal injury after limb ischemia-reperfusion (I/R) injury, to elucidate the mechanisms of the Toll-like receptor 4 (TLR 4)/NF-κB signaling pathway using histopathological and immunohistochemical methods. Methods Male Sprague-Dawley rats were randomly assigned to five groups (numbered from 1 to 5): the sham group (Group 1, only the anesthesia procedure was conducted without limb I/R), the I/R group (Group 2, 4 h of reperfusion was conducted following 4 h limb ischemia under anesthesia), the I/R + I-postC group (Group 3, 4 h of ischemia and 4 h of reperfusion was conducted; before perfusion, 5 min of limb ischemia and 5 min of reperfusion were performed in the rats and repeated 3 times), the I/R + TAK group (Group 4, rats were injected with TLR4 antagonist TAK through the caudal vein before limb ischemia and reperfusion under anesthesia), the TAK group (Group 5, rats were injected with TAK, and the anesthesia procedure was conducted without limb I/R). Histological changes in the kidney in different groups were observed, and the extent of tubular injury was assessed. Changes in biochemical indexes and the expression of inflammatory factors, TLR4, and NF-κB were also evaluated. Results Compared with rats in the I/R group, the secretion of inflammatory factors and the expression levels of TLR4 and NF-κB were decreased in rats in the I/R + I-postC group. Histological analysis revealed renal injury, including inflammatory cell infiltration, dilatation of the tubuli lumen, congestion in glomerular capillaries, degeneration of tubuli epithelial cells, and necrosis was ameliorated by I-postC. Immunohistochemical studies showed that I/R-induced elevation in TLR4 and NF-κB expression was reduced by I-postC treatment. Moreover, the expression levels of TLR4, NF-κB, and inflammatory factors in rats in the I/R + TAK group were also decreased, and the renal pathological lesion was alleviated, which was similar to that in rats in the I/R + I-postC group. Conclusions The present findings suggest that I-postC can reduce tissue injury and kidney inflammation induced by limb I/R injury, possibly via inhibition of the TLR4 and NF-κB pathways.

Effect of dexmedetomidine on tourniquet-induced skeletal muscle injury

“…TLR4 can activate NF-κB signaling, initiating the transcription of many pro-inflammatory genes 13,14 . Consistent with a previous report, we observed significantly higher expression of TLR4 and NF-κB in the I/R group compared with the sham group 15 , indicating an important role for TLR4/NF-κB pathway activation in the pathophysiology of skeletal muscle I/R injury. Moreover, levels of TLR4 and NF-κB in skeletal muscle were significantly lower in mice treated with Dex compared with untreated mice after I/R.…”

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

“…NF-κB was found to be a transcriptional activator of HIF-1α, linking ischemia to innate immunity and inflammation [ 104 ]. Inhibition of TLR4 and NF-κB pathways was involved in amelioration of acute kidney injury induced by limb ischemia/reperfusion [ 118 ]. Similar results were reported in lung injury induced by limb ischemia where suppression of TLR-4 and NF-κB had a protective effect [ 119 ].…”

Cerebral protection by remote ischemic post-conditioning in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials

“…Ischemic post-conditioning has been shown to reduce IRI in several vital organs ( 5 , 34 , 35 ). It can protect the brain from IRI and improve neurological deficits through a variety of endogenous protective mechanisms.…”