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BACKGROUND: In clinical, propofol can contract cerebral vessels, decrease cerebral blood flow, decrease brain metabolic oxygen consumption,which can decrease pressure in brain. Studies prove that propofol can protect endothelial cell that may be injuried by active oxygen injury and also decrease nerves injury of experimental rats with cerebral ischemia.OBJECTIVE: To investigate the protective effects of propofol on cerebral ischemia-reperfusion injury in rat and its mechanism.DESIGN: Randomized and controlled study.SETTING:Anesthesiological Department of the Second Affiliated Hospital of Xi'an Jiaotong University.PARTICIPANTS: The experiment was conducted at Pharmacological Laboratory of Medical College of Xi' an Jiaotong University in 2004. Totally 40 healthy male SD rats, aged 3-4 months, weighting 200-300 g, were divided randomly into four groups: Model group, control group, nimodipine group and propofol group, with 10 in each group.METHODS: The rats were anesthetized by intraperitoneal methods with ketamine and propofol separately. When righting reflex was abolished, external carotid artery was separated and ligated. A nylon thread was put at the stump site of external carotid artery without ligation. Model group: 10 mL normal saline was injected into intraperitone in 10 minutes before ischemia.Control group: 10 mL normal saline was injected into intraperitone at the end of operation. Nimodipine group: 10 g/L nimodipine (1 mg/kg) was injected into intraperitone in10 minutes before ischemia. Propofol group: 10 g/L propofol (110 mg/Kg) was injected into intraperitone in 10 minutes before ischemia. When ischemia was lasted for 3 hours, nylon thread was with drawed for reperfusion. When reperfusion was lasted for 3 hours, blood samples were obtained from orbit. Skulls were opened and brains were removed.Effect of propofol on cerebral ischemia-reperfusion injury was observed.MAIN OUTCOME MEASURES: Infarction area, cerebral water content,serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, brain superoxide dismutase (SOD) activity, malondialdehyde (MDA) and Ca2+levels were measured. Ultrastructure of brain tissue was examined under electron microscope.RESULTS: ①Infarct area in propofol group was significantly smaller than that in model group [(10.45±3.65, 19.68±4.03)%, (t=3.493,P ＜ 0.01)]. ② CK level was lower in propofol group than that in model group [(471±200,1 930±917) IU/L, (t=3.493, P ＜ 0.01)]; and LDH level in propofol group [(8 240±2 580) U/L] was significantly different from that in model group [(15 470±2 680) U/L, (t=3.441, P ＜ 0.01)]; And water content in brain tissue was lower in propofol group than that in model group [(78.2±2.4,82.9±2.9)%, (t=3.321, P ＜ 0.01)]. ③ The death rate of rats was 13.6%in propofol group, and 47.6% in model group, the former was decreased obviously as compared with the latter, and the difference was significant (t=6.21,P ＜ 0.05). ④ SOD activity was (1 690±780) U/g in propofol group and (830±110) U/g in model group, the difference was significant (t=3.420, P ＜ 0.01); but MDA content was obviously lower in propofol group than that in model group [(0.058±0.014, 0.115±0.047) μmol/g, (t=3.336, P ＜ 0.01)].CONCLUSION: Propofol has protective effect on cerebral ischemia-reper fusion injury in rats, and the mechanism is related with inhibition of Ca2+overloading and lipid peroxidation.
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Objective To study the protective effects of propofol against ischemia-reperfusion injury in rat brains.Methods Modified Longa modle of focal cerebral ischemia-reperfusion injury was used. 200 healthy male SD rats, weighing 200-300g were anesthetized with intraperitoneal(I.P.) ketamine and propofol. When righting reflx was abolished, external carotid artery was exposed. A nylon thread with rounded end was inserted cranially until anterior cerebral artery was reached. After 3h ischemia nylon thread was withdrawn for reperfusion which lasted 3h. Bloos samples were obtained from orbit. Skull was opened and brain removed. In control group carotid artery was exposed but nylon thread was not inserted cranially. The animals were divided into four groups: (1)ischemia-reperfusion model group: normal saline 10 ml was administered I.P.,(2)operation control group: normal saline was given I.P.at the end of operation,(3)nimodipine group: nimodipine 1 mg?kg -1 was administered I.P. 10 min before ischemia,(4) propofol group: propofol 110 mg?kg -1 was given I.P. 10 min before ischemia. Brain infarction area, cerebral water content, serum lactate dehydrogenase(LDH) and creatine kinase(CK) levels,brain SOD activity and MDA and Ca 2+ levels were measured. Ultrastracture of brain tissue was examined by electron microscopy.Results Propofol 110 mg?kg -1 reduced mortality after brain ischemia/reperfusion injury. Infarction area of brain was significantly smaller in propofol and nimodipine groups than that in group 1. Propofol significantly inhibited the increases in serum LDH and CK levels induced by ischemia/reperfusion, increased SOD activity and decreased MDA content and Ca 2+ level in brain tissue. There was less brain tissue damage in propofol group.Conclusions Propofol 110 mg?kg -1 has protective effect against cerebral ischemia-reperfusion injury in rats.
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Objective To investigate the protective effect of fructose 1,6-diphosphate (FDP) on the brain against ischemia-reperfusion (I/R) injury and the possible mechanism. Methods One hundred and eighty SD rats weighing 275-325 g were randomly divided into 3 groups (n = 60 each): Ⅰ gham operation group; Ⅱ I/R group and Ⅲ FDP group. Global cerebral I/R was produced by 4-vessel technique. Bilateral vertebral arteries were coagulated and bilateral common carotid arteries were occluded for 5 min and then released for reperfusion. In sham operation the four vessels were exposed but not occluded. In FDP group FDP 1.5 mg?kg-1 was given Ⅳ when reperfusion was started, while in sham-operation group and I/R group normal saline (NS) 1.5 ml?kg-1 was given Ⅳ instead of FDP. The animals were killed at 2, 6, 12, 24, 48 and 72 h of reperfusion ( n = 5 each) for determination of cerebral SOD activity and MDA contents, the number of apoptotic neurons (TUNEL) and expression of P38 and Ref-1 in the brain (immuno-histochemical method) .Results The MDA content was significantly higher whereas the SOD activity and P38 and Ref-1 expression were significantly lower at all time points in I/R group than in sham operation group ( P