MO_IV_L: Molecular Sciences IV. Lectures
A. R. Toth1,2; T. Lakat1,2; A. Hosszu1,2; A. Molnar2; K. Demeter3; H. Kelemen2,3; A. J. Szabo2,4; A. Dénes5; M. Szabo2; E Mikics6; A. Fekete1,2
1SE Diabetes Research Group, Budapest
2Semmelweis University 1st Department of Pediatrics, Budapest
3Behavioral Studies Unit, Institute of Experimental Medicine, Budapest
4SE Pediatrics and Nephrology Research Group, Budapest
5ELKH-Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest
6ELKH-Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Budapest
Perinatal asphyxia (PA) leads to the death of more than half million mature newborns yearly. It is associated with several serious complications including hypoxic encephalopathy, renal- hepatic- and cardiovascular injury, as well as respiratory distress. However, the extent of PA-associated renal damage is not clarified yet, pathomechanisms are little known. In addition, adults previously affected by PA may be more vulnerable in conditions where ischemia/reperfusion (IR) injury occurs, such as transplantation, major surgeries, infarction or sepsis.
The aim of the present study was to determine short- and long-term renal damage after PA and to investigate susceptibility to IR injury in adulthood.
7 day-old male Wistar rats (n=5-10/group) were separated from the dam and incubated in 4% O2; 20% CO2 in N2 gas mixture for 15 minutes. Control animals were incubated in normal air. Samples were collected after 24 hours, 6 weeks and 6 months. At the age of 6 months, 35 min bilateral renal IR insult was performed on both control and PA rats. Serum levels of electrolytes and renal parameters were determined. Highly selective tubular injury markers (Kim1, Ngal) were measured. Expression of hypoxic (Hif1α, Hif2α), inflammatory (Il1α, Il1β), apoptotic (Bax, Bcl-2), angiogenic (Vegf, Epo) and profibrotic (Tgfβ, Pdgf) genes were investigated. Periodic-Acid Schiff staining and anti-CD68 labeling were performed on kidney tissue sections.
Tubular injury markers and heat shock protein expressions increased, inflammatory, angiogenic and fibrotic pathways were activated in the kidney 24 hours following PA. At the age of 6 months serum creatinine levels were elevated, suggesting long-term impact of PA. PA rats were more sensitive to renal ischemic insult, confirmed by higher serum creatinine, as well as increased renal expressions of Ngal, Hif1α, Epo.
Short- and long-term renal damage following PA were observed. In addition, birth asphyxia may increase sensitivity to renal injury even in adulthood, which may be worth considering in clinical situations with potential renal impairment such as major surgeries. The molecular pathways described here are potential targets for therapeutic intervention.
Funding: 2017-1.3.1-VKE-2017-00006, OTKA (FK124491, PD131637, K135398), 2020-4.1.1.-TKP2020-(6183069269, 6183169273), ÚNKP-20-4-II-SE-13
Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine