The effects of propofol on hippocampal caspase-3 and Bcl-2 expression following forebrain ischemia-reperfusion in rats.
Transient cerebral ischemia may result in neuronal apoptosis. During this process, several apoptosis-regulatory genes are induced in apoptotic cells. Among these genes, cysteinyl aspartate-specific protease-3 (caspase-3) and B-cell leukemia-2 (Bcl-2) are the most effective apoptotic regulators because they play a decisive role in the occurrence of apoptosis. Research has shown that propofol, which is an intravenous anesthetic agent, exhibits neuroprotective effects against cerebral ischemia-reperfusion injury, although the neuroprotective mechanism is still unclear. In this study, we examined the effects of propofol in rats after forebrain ischemia-reperfusion. We assessed the expression of hippocampal caspase-3, which acts as an apoptotic activator, and Bcl-2, which acts as an apoptotic suppressor. Forebrain ischemia was induced in hypotensive rats by clamping the bilateral common carotid arteries for 10 min. Propofol was administered via a lateral cerebral ventricle injection using a microsyringe after the induction of ischemia. Neuronal damage was determined by histological examination of brain sections at the level of the dorsal hippocampus. Caspase-3 and Bcl-2 expression in the hippocampus were detected using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We also used an immunohistochemical method after ischemia-reperfusion. In the hippocampus, caspase-3 and Bcl-2 mRNA were dramatically increased at 24h after forebrain ischemia. Following 6-24h of reperfusion, forebrain ischemia for 10 min induced a gradual increase in the expression of caspase-3 and Bcl-2 protein in the rat hippocampus, which peaked at 24h. In the propofol (1.0mg/kg) intervention group, the hippocampal expression of caspase-3 mRNA decreased significantly in rats 24h after ischemia; Bcl-2 mRNA was increased at the same time point. During the 24-h reperfusion period and after treatment with propofol, the level of caspase-3 protein expression was low, while the level of Bcl-2 was high. Thus, our results suggest that the neuroprotective effects of propofol against neuronal apoptosis may be mediated by the inhibition of caspase-3 expression and an increase in Bcl-2 expression.
Li
Jun
J
Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, 150001 Harbin, China.
Han
Baoqing
B
Ma
Xuesong
X
Qi
Sihua
S
D018686:Anesthetics, Intravenous / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology
D018686:Anesthetics, Intravenous; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D015742:Propofol