The Effects Of PKC Epsilon Selective Inhibitor On Endothelial Factors And Endoplasmic Reticulum Stress Related Protein In The Psychologically Stress Rats

OBJECTIVE To establish psychologically stress rat model,using randomly empty bottle stimulation.After an intraperitoneal injection of protein kinase C(PKC)inhibitor(PKC-[?]V1-2 peptide).The effects of psychological stress on some endothelium-derived factors and the relationship between psychological stress and endoplasmic reticulum stress were studied.The intervention of PKC-[?]V1-2 peptide on endothelium-derived factors and endoplasmic reticulum stress in the states of psychological stress were explored,from that animal experimental data was gained for exploring the effective mechanism of PKC inhibitors on cardiovascular disease.METHODS(1)Establish psychologically stress model:The experimental rats were divided randomly into control group(C group),model group(M group)and PKC-[s]V1-2 peptide group(P group),10 rats for each group,half male and half female.After 7 days adjustment period during which water supply was regular(experimental 1th-7th),then the experiment turned to modeling period(experimental 8th-22th).The P group and M group were accepted unregular water supply/empty bottle stimulation according to a random number table,and P group was injected intraperitoneally with PKC-[?]V1-2 peptide(2mg/kg,once/day)and M group with saline(2mL/kg,once/day),while the control group was still accepted regular water supply per day and injected with saline(2mL/kg,once/day).(2)Detect the experimental parameters:In the modeling ending day(experimental 23th),the behavior of rats were evaluated by an open-field test.The levels of plasma stress hormone adrenaline(Adr),cortisol(COR)were measured,as well as the content of endothelial factors endothelin-1(ET-1),tissue plasminogen activator(t-PA)and plasminogen activitor inhibitor-1(PAI-1)by ELISA.The expression of GRP78 and Caspase12 were evaluated by Western Blot.RESULTS Compared with the C group,the open-field test scores and the levels of ET-1 in both M and P group were significantly higher(p<0.05),while there is not significantly different between P and M group(p>0.05).The levels of plasma COR,Adr,PAI-1 and the expression levels of vascular endoplasmic reticulum stress related protein GRP78 and Caspase12 in the M group was significantly higher,while the level of plasma t-PA and the ratio of t-PA and PAI-1 were significantly lower than the C group,and the levels of plasma COR,Adr,PAI-1 and the expression levels of vascular endoplasmic reticulum stress related protein GRP78 and Caspase12 in the P group was significantly lower,while the level of plasma t-PA and the ratio of t-PA and PAI-1 were significantly higher than the M group(p<0.05),whereas there is no significantly different between P group and C group(p>0.05).CONCLUTION PKC ? inhibitor can adjust the change of endothelium-derived factor level and inhibit the endoplasmic reticulum stress induced by psychological stress.