Effects of tanshinone II A on the level of brain NMDAR1 protein in rats after cardiopulmonary resuscitation and its protection towards brain function

Abstract

Objective To investigate the impact of tanshinone Ⅱ A on the level of brain NMDAR1 protein in rats after cardiopulmonary resuscitation and its effects of brain function protection.Methods Seventy-eight SD male rats were randomly (random number) divided into three groups:group A (sham group,n =6),group B (control group,n =36) and group C (Tanshinone Ⅱ A intervention group,n =36).All animals were induced to be models of cardiac arrest by choking.The rats of group C received intravenous injection of Tanshinone Ⅱ A in dose of 15 mg/kg immediately at initiation of resuscitation,while rats of group B were intravenous injected same amount of normal saline instead.Brains tissues of all rats were taken at 1,6,12,24,48 and 72 h after the restoration of spontaneous circulation (ROSC).Immunohistochemical staining method was applied for measuring the levels of brain tissue NMDAR1 and Caspases-3,while water content of the brain was detected by wet and dry weight ratio.The experimentaldata were analyzed by using one-way ANOVA.Results (①)The level of brain NMDAR1 protein in group B increased at 1 h and reached its peak at 6 h after ROSC,then its level gradually declined and dropped below normal at 48 h,72 h,and there were significant difference in variation of NMDAR1 protein levels in comparison with the group A (P ＜ 0.05) ; the NMDAR1 protein levels at 1,6,12 h in group C were significantly lower than those in group B at the same intervals (P ＜ 0.01),but no significant differences were seen at 24,48,72 h (P ＞ 0.05).(②)The level of brain Caspases-3 in group B increased after ROSC,and reached its peak at 48 h after ROSC,then declined and maintained above normal at 72 h,and this variation was significantly different from that of the group A (P ＜ 0.01) ; while the levels of caspase-3 at 1,6,12,24 h in group C were significantly lower than those in group B (P ＜ 0.01),but thses differences at 48,72 h were still significant (P ＜ 0.05).(③)The water content of brain tissue in group B increased at 1 h and reached its peak at 24 h after ROSC,then gradually decreased from 48 h,but maintained above normal at 72 h,and this trend of variation was significantly different from that of group A (P ＜ 0.01 or P ＜ 0.05).Compared with group B,water content of brain tissue in group C decreased more significantly (P ＜ 0.01).Conclusions Tanshinone Ⅱ A down-regulates brain NMDAR1 protein level at early stage in rats as well as significantly inhibits the level of Caspases-3 thereby ameliorating brain edema after cardiopulmonary resuscitation. Key words: Tanshinone Ⅱ A ; NMDAR1 ; Caspases-3 ; Brain edema; Cardiac arrest; Cardiopulmonary resuscitation; Rats