Investigation Of The Relationship Between Cathepsin B-Mediated Apoptosis And P38MAPK Signaling Pathway After Cerebral Ischemia-Reperfusion In Rat

Background and Objective:Apoptosis will occur at the ischemic penumbra after cerebral ischemia andreperfusion.Studies have found that P38MAPK, Cathepsin B all involved in thisprocess. We use the Cathepsin B inhibitor CA-074in ischemia-reperfusion model todetect the P-P38and Cathepsin B protein expression and find the relationship betweenthem.Methods:56rats,male,weight280±20g,10-12weeks,clean level health, were dividedinto shaml group (n=6), cerebral ischemia and reperfusion model group(n=25) andCA074interention group (n=25). Each group are then divided into2h,6h,12h,24h,four subgroups according to reperfusion time.There are5rats in2h,6h,12hroups,10rats in24h.The lateral ventricle injection method is given20ugCA-074for theintervention group or1ulDMSO for the model group, line switch for the legal systemof rats MCA occlusion (MACO) model after the lateral ventricle injection.By usingthe neural function score standard to evaluate the nervous function; using TTCdyeing to detect cerebral infarction volume change; immunohistochemical method tomeasure cerebral cortex P-P38and Cathepsin B protein expression; tunel method tomeasure brain cortex cell apoptosis change.Results:1.TTC results: the relatively infarction volume in24h model group:24.73±0.97％，the relatively infarction volume in24h CA-074model group:13.46±0.64％(p<0.05)。2. The level expression of P38MAPK in ischemic brain tissue:sham group: no significant P-P38immune activity expression；model group:2h, a small amount of p-P38,6h,reached its peak,12h,24h,reduced a little；the intervention group: all timepoints over the same period with less than the model group(p<0.05).3.The level expression of Cathepsin B in ischemic brain tissue；sham group: nosignificant P-P38immune activity expression；model group:2h, a small amount of p-P38,6h,reached its peak,12h,24h,reduced a little；the intervention group: all timepoints over the same period with less than the model group(p<0.05).4.The result of TUNEL:Sham group: a few apoptotic cells；model group:time-dependent manner,after2h a few apoptotic cells can be seen,and it increased atthe highest in24h;the intervention group: apart of2h time points over the same periodwith less than the model group(P<0.05).Conclusion:The lysosome Cathepsin B may mediated through cell apoptosis by P38MAPKsignaling pathways.