Effects of mild hypothermia on Bcl-2 and Bax gene expression in ischemic brain of rats

doi:10.3321/j.issn:1673-8225.2003.22.015

Abstract：AIM:To investigate the effects of mild hypothermia of different durations on neuronal apoptosis and expressions of Bcl-2 and Bax genes in rat models of middle cerebral artery occlusion (MCAO). METHODS:Forty Sprague Dawley rats were divided randomly into 5 equal groups,namely sham- operation group (group A),normothermic ischemic controls (group B),30- min mild hypothermia group (group C),1- hour mild hypothermia group (group D),and 3- hour mild hypothermia group (group E).MCAO models were established by Longa's method,and reperfusion was allowed after 3- hour occlusion.Mild hypothermia for 0.5,1.0 and 3.0 hours respectively were initiated at the start of occlusion,and at the 24th hour of subsequent reperfusion,the rat brain were removed and continuously sectioned for TUNEL staining,Bcl- 2 and Bax immunohistochemical staining respectively. RESULTS:Apoptotic neurons (TUNEL- positive) were identified primarily in the cortex of the frontal and parietal lobes and peri infarct striatum, where Bcl- 2- and Bax positive cells were also spotted,in similar distribution pattern to that of TUNEL positive cells.Compared with the control group, the percentage of Bcl- 2 positive cells was significantly higher in group E (23.0± 3.8,P< 0.05), while the percentage of Bax positive cells was lowered in both groups D and E (45.9± 4.1, P< 0.05; 32.4± 3.7,P< 0.01, respectively).Inverse correlation was noted between the apoptotic rate and the Bcl- 2 to Bax protein ratio (r=- 0.975 9,P< 0.01). CONCLUSION:Mild hypothermia lasting more than 1.0 hour inhibit cellular apoptosis, the occurrence of apoptosis is determined by Bcl- 2 to Bax protein ratio.