title: Protective effects of propofol against whole cerebral ischemia/reperfusion injury in rats through the inhibition of the apoptosis-inducing factor pathway.
abstract: Cerebral ischemia/reperfusion (I/R) injury could cause neural apoptosis that involved the signaling cascades. Cytochrome c release from the mitochondria and the followed activation of caspase 9 and caspase 3 are the important steps. Now, a new mitochondrial protein, apoptosis-inducing factor (AIF), has been shown to have relationship with the caspase-independent apoptotic pathway. In this study, we investigated the protective effects of propofol through inhibiting AIF-mediated apoptosis induced by whole cerebral I/R injury in rats. 120 Wistar rats that obtained the permission of the animal care committee of Harbin Medical University were randomly divided into three groups: sham group (S group), cerebral ischemia/reperfusion injury group (I/R group), and propofol treatment group (P group). Propofol (1.0mg/kg/min) was administered intravenously for 1h before the induction of ischemia in P group. The apoptotic rate in three groups was detected by flow cytometry after 24h of reperfusion. The mitochondrial membrane potential (MMP) changes were detected via microplate reader. The expressions of B-cell leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and AIF were evaluated using Western blot after 6h, 24h and 48h of reperfusion. The results of our study showed that apoptotic level was lower in P group compared with I/R group and propofol could protect MMP. The ratio of Bcl-2/Bax was significantly higher in P group compared with I/R group. The translocation of AIF from mitochondrial to nucleus was lower in P group than that in I/R group. Our findings suggested that the protective effects of propofol on cerebral I/R injury might be associated with inhibiting translocation of AIF from mitochondrial to the nucleus in hippocampal neurons.
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Wan-Chao
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Xian-Zhang
authors.initials: XZ
authors.lastname: Zeng
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: scy-zw@163.com.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Zi-Yong
authors.initials: ZY
authors.lastname: Yue
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; C000617196:Bcl2 protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015742:Propofol
keywords: AIF; Apoptosis; Brain rrotection; Ischemia/Reperfusion injury; Propofol