Ischemic conditioning by short periods of reperfusion attenuatesrenal ischemia/reperfusion induced apoptosis and autophagy in therat

摘要

Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy.We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during aprolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated theantioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar ratssubjected to sham control, 4 stages of 15-min IC (I15 x 4), 2 stages of 30-min IC (I30 x 2), and total60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay,monitoring O_2~-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hoursof reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level andproapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome Crelease, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments,microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequentlytubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level.I30 x 2, not I15 x 4 decreased ROS production and cytochrome C release, increased Manganesesuperoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalaseexpression and provided a more efficient protection than I60 against IR induced tubular apoptosisand autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renalischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys.Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content,increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renaltubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in ratkidneys.