Hypoxic Preconditioning To Reduce Ischemia - Reperfusion Brain Damage In Apoptosis And Related Protein Expression Changes

The effect of Hypoxic Preconditioning on apoptosis and expression of protein related to apoptosis in rats during focal cerebral ischemia /reperfusion injuryOBJECTION: To study the Neuroprotective effects and molecular mechanism of Hypoxic Preconditioning on reperfusion injury following ischemia.METHODS: The rats with MACO was described by Longa for 3h and reperfusion for 24h. 48 rats were divided randomly into 3 groups that were the sham group, ischmia/reperfusion (I/R) and Hypoxic Preconditioning group(HP+I/R). The neurological deficit (I1h,I2h,I3h,R1h,R4h,R8h,R24h)was measured by Longa's method and the ability of learning and remembrance after reperfusion 24h was measured by Y-labyrinth. The immunohistochemistry staining and TUNEL reaction were used to facilitate the quantities of Survivin,fas/fas-L and HSP-70 protein and apoptosis in the brain tissus.RESULTS:(1)The neurological score and the study- remembrance score(N represents number of time when the rat learn standardization ,A/10 represents rate of retention of memory ) after ischmia 3 hours and reperfusion 24h (I 3h / R 24h) was 0, 47.5±7.1, 0.91±0.08 in the sham operation; 1.1±0.6, 86.3±9.2, 0.54±0.14 in the I/R group; 0.4±0.5, 66.3±7.4, 0.66±0.09in the HP+I/R group.(2)There were 14.0±2.1 Survivin immunostaining cells per high power field (HPF) in the I/R group , 27.1±4.2 cells/ HPF in the HP+I/R group,and 0.6±0.9 cells / HPF in sham group.(3)There were 27.3±2.8 fas immunostaining cells per high power field (HPF) in the I/R group , 11.1±2.2 cells/ HPF in the HP+I/R group,and 0.8±1.2 cells / HPF in sham group.(4)There were 24.6±3.6 fas-L immunostaining cells per high power field (HPF) in the I/R group , 9.6±1.7 cells/ HPF in the HP+I/R group,and 0.5±0.8 cells / HPF in sham group.(5)There were 0.3±0.5 HSP-70 immunostaining cells per high power field (HPF) in sham group, 26.3±3.6 cells/HLP in the I/R group,and 47.0±3.1 cells /HPF in the HP+I/R group.(6) The number of apoptosic cells per high power field (HPF) is 39.4±2.4 in the I/R group , 23.1±4.4 cells/ HPF in the HP+I/R group,and 0.5±0.7 cells / HPF in sham group. The difference among HP+I/R group and control groups(I/R,Sham) was significant (P<0.05).CONCLUSION: Hypoxic Preconditioning can protect the ischemia brain on reperfusion injury , reduce the neurological deficit and promote rehabilitation of learning and remembrance of rats . Down-regulating the expression of fas/fas-L , up-regulating the expression of Survivin,HSP-70 protein and reducing apoptosis of nerve cell would be one of the molecular mechanism.