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


METHODS
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 3 h; While M group rats received calpain inhibitor 10 mg/kg via the tail vein intravenously at 30 min before the animals inhaled 3 % sevoflurane for 3 h, subsequently received MDL 28170 3.33 mg/kg/h for 3 h. Sev group rats were only exposed to 3 % sevoflurane for 3 h 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.


RESULTS
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 76/80 kDa ratio of μ-calpain were significantly decreased in M group on the 1st day.


CONCLUSIONS
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.
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China.
Xiang
X
Liu
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China.
Xueyin
X
Song
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China.
Tianbao
T
Yuan
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China.
Jihua
J
He
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China.
Xiuli
X
Wang
Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China. 18032288937@163.com.
Qiujun
Q
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002154:Calpain / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D008738:Methyl Ethers / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D008738:Methyl Ethers; D000077149:Sevoflurane; D002154:Calpain; C449002:mu-calpain
Aged; Apoptosis; Calpain; Hippocampal; Sevoflurane