Protective effects of propofol on focal ischemia-reperfusion injury in rats

Yingmin CAI; Haitao HU; Meina WANG; Xiaoya MA

ABSTRACT

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.