Аннотация:There are not so many approaches for treatment of acute kidney
injury (AKI) which is a high-mortality disease affecting approximately
a third of intensive care units patients. We investigated the
nephroprotective possibility of two different methods, namely
ischemic preconditioning (IPC) and dietary restriction (DR), and
evaluated the role of autophagy and mitophagy in mechanisms of
damage and protection of ischemic kidney. While the majority of
patient with AKI are elderly, all parts of the research were performed
in young and old animals.
IPC consisted of 4 cycles, including 15 seconds of ischemia and
15 seconds of reperfusion, immediately before the 40 minutes
ischemia. DR was performed for 4 weeks by limiting the amount of
food to 65% of the daily intake. Both methods, IPC and DR, attenuated
AKI induced by ischemia/reperfusion (I/R), but only in young rats. In
old animals, those approaches were unable to decrease the levels of
serum creatinine and blood urea nitrogen.
To unravel mechanisms underlying those effects, we evaluated
the activation of the autophagic-lysosomal system in kidney tissue.
We have shown that in young rats with IPC, fluorescence intensity of
LysoTracker Green was not as increased as in the group with I/R
alone. However, in old rats we observed the increase only in the
group with IPC. Similarly, DR significantly increased LysoTracker
Green fluorescence intensity and LC3II/LC3I ratio in young rats, but
there were no such alterations in old rats.
Impaired mitochondrial quality control was demonstrated by
analysis of mitochondrial transmembrane potential by flow cytometry.
A fraction of low-potential mitochondria was found in old
kidneys and this de-energized population was even increasing after
IPC in old, but not in young rats. Ineffectiveness of mitophagy was
also suggested by the evaluation of the PINK-1 level in mitochondria.
Supported by RSF grants 18-15-00058 (analysis of AKI, DR and
mitophagy) and 14-15-00147 (study of IPC).