Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis.

Abstract

Sevoflurane is one of the most commonly used volatile anesthetics and it has been shown to induce widespread apoptotic neurodegeneration in aged rat. Calpain is also activated during apoptosis in several types of cells. We hypothesized that calpain resulted in apoptosis under long time sevoflurane exposure, and it might play a role in the sevoflurane-induced memory impairment in aged rats. Seventy-two 18-month-old male Sprague-Dawley rats were randomly divided into three groups (n=24): Control group rats were exposed to simply humid 50% O2 balanced by N2 for 3h; While M group rats received calpain inhibitor 10mg/kg via the tail vein intravenously at 30min before the animals inhaled 3% sevoflurane for 3h, subsequently received MDL 28170 3.33mg/kg/h for 3h. Sev group rats were only exposed to 3% sevoflurane for 3h without calpain inhibitor. Morris Water Maze was used to test the ability of learning and memory. Cytosolic calcium concentration was measured by using flow cytometry. Annexin-V labeled with a fluorophore or biotin can identify apoptotic cells by binding to PS. The expression of calpain in the hippocampus of rats was tested by Western blots. The results showed that the M group had a shorter latency and had a larger number of times crossing over the previous platform site than that of the Sev group. Compared with Sev group, apoptosis rate and 76/80kDa ratio of μ-calpain were significantly decreased in M group on the 1stday. Sevoflurane might induce apoptosis through increasing [Ca(2+)]c and the activity of μ-calpain, which might be identified at least partially the molecular mechanism by which sevoflurane induces apoptosis.