Irbesartan Pretreatment On Ischemia-reperfusion Effects And Mechanism Of The Rat Blood-brain Barrier

Part 1 Effects of Irbesartan on the water content of brain tissue and the expression of aquaporin-4 and IgG after cerebral ischemia-reperfusion in ratObjective: To study the effects of Irbesartan on the water content of brain tissue and the expression of IgG and aquaporin-4 after cerebral ischemia-reperfusion in rats.Method: The experimental SD rats were pretreated with Irbesartan by intragastric administration. Twenty-one days later, CI/R model was established following the modified Longa's method. After ninety minutes-ischemia and at 2h or 48h after reperfusion, the water content of rat brain tissue was detected, at the same time, the expression of IgG and AQP4 were detected by immunochemistry.Results: (1)Compared to sham-operated groups, the water content of brain was highly increased in CI/R control groups at both time points(P<0.01).Compared to CI/R control groups, pre-treatment with Irbesartan could reduce the water content of brain, which was more significantly in high dose treated groups(P<0.05～0.01).(2) Two hours after reperfusion, there were no significant difference among groups in expression of IgG. Forty-eight hours after reperfusion, compared to sham -operated groups, the expression of IgG was markedly increased(P < 0.01). Compared to CI/R control groups, pre-treatment with Irbesartan could reduce the IgG expression, which was more significantly in high dose treated groups(P<0.05～0.01). (3)Compared to sham-operated groups, the expression of AQP4 was up-regulated in CI/R control groups at both observation time point(sall P <0.01).Compared to CI/R control groups, pretreatment with high dose Irbesartan could up-regulate the expression of AQP4 at both time points(P<0.01, and also in low dose treated group at 48h(P<0.01), but not in low dose treated group at 2h.Conclusions: After the CI/R injury, the water content of brain tissue, expression of IgG and AQP4 were highly up-regulated; Pretreatment with Irbesartan could significantly improve these abnormalities,and protect from brain edema, perhaps by up-regulating AQP4 expression.Part 2 Effects of pretreatment with Irbesartan on expression of AQP4mRNA and PKC activity after cerebral ischemia reperfusion in rats.Objective:To investigate the effects of pretreatment with Irbesartan on expression of AQP4mRNA and PKC activity around the ischemic core tissue in rats after cerebral ischemia reperfusion.Methods:The experimental SD rats were pretreated with Irbesartan by intragastric administration. After pretreatment for twenty-one days, CI/R model was established by using the modified Longa's method. After ninety minutes-ischemia and at 2h or 48h after reperfusion, AQP4mRNA level in brain tissue was detected by RT-PCR, and the respective PKC activity was measured by PepTag? Assay for Non-Radioactive Detection of Protein Kinase C.Results:(1)AQP4mRNA was higher expressed in CI/R control group than that in sham-operated group at both time point of 2h and 48h(all P<0.05); Compared to control groups, AQP4mRNA was higher in low dose irbesartan-treated group at 48h(P<0.05), but no difference was found at 2h between them; At both time points AQP4mRNA level was higher in high-dose treated Irbesartan group than that in CI/R control group(all P<0.05);Compared to low-dose treated groups, AQP4mRNA level in high-dose treated group was higher at 48h, but no difference was found between them at 2h.(2)At both time points, the protein kinase C activity was enhanced in CI/R control groups(P<0.01); Compared to CI/R control groups at both time points, PKC activity was reduced significantly in both Irbesartan treated groups(P<0.05～0.01);Compared to low-dose Irbesartan treated group, PKC activity was lower in high-dose Irbesartan treated group at 48h after reperfusion, but no difference was found between them at 2h after reperfusion.(3)At every time point, AQP4mRNA showed negative correlation with PKC activity in CI/R groups.Conclusions:After CI/R injury, AQP4mRNA expression was enhanced, and protein kinase C was activated; Pretreatment with Irbesartan could enhanced the AQP4 mRNA expression, which may be through inhibiting the activation of protein kinase C partially.