Protective Effects Of Penehyclidine On Cerebral Injury Induced By Cardiopulmonary Bypass Of Rats

Objective: To investigate the Protective effects of Penehyclidine on cerebral injury induced by Cardiopulmonary Bypass(CPB) of Rats and its mechanism.Methods: Forty male adult Sprague-Dawley rats were randomly divided into five groups : Group S served as control group without CPB ;The rats of group C were underwent 60 minutes of CPB and were observed 2 hours later; The rats of group PL,PM and PH received 0.2,0.6 and 2 mg·kg-1 Penehyclidine respectively in priming solution except CPB and survived 2 hours. Venous blood was collected at the end of CPB(T1)and 2 hours after the end of CPB(T2). Plasma levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were detected by radioimmunoassay . Plasma levels of S-100? protein were detected by enzyme-linked immunosorbent assay . Expression of occludin and ZO-1 were determined by western blotting. Ultrastructure of hippocampus and blood brain barrier was observed under trans-electron microscope.Results: Compared with group S , the level of plasma inflammatory mediator TNF-αof group C,PL,PM and PH increased(P<0.05)at both time of T1 and T2. Compared with group C, the level of plasma TNF-αof group PL,PM and PH decreased at both time of T1 and T2, and the difference at T1 had statistics significance(P<0.05). Compared with group PM, the level of plasma TNF-αof group PH decreased at both time of T1 and T2, and the difference at T2 had statistics significance(P<0.05). Compared with group S , the level of plasma IL-6 of group C,PL,PM and PH increased(P<0.05)at both time of T1 and T2. Compared with group C, the level of plasma IL-6 of group PL,PM and PH decreased at both time of T1 and T2 (P<0.05). Compared with group PM, the level of plasma IL-6 of group PH decreased at the time of T1 and T2(P<0.05).Compared with group S , the plasma level of S-100? of group C,PL,PM and PH increased(P<0.05)at both time of T1 and T2. Compared with group C, the plasma level of S-100? of group PL,PM and PH decreased at both time of T1 and T2(P<0.05). Compared with group PM, the plasma level of S-100? of group PH decreased at both time of T1 and T2, and the difference at T1 had statistics significance(P<0.05).CPB decreased the expression of occludin and ZO-1 of blood-brain barrier in rats. Compared with group S, group C and PL had significant differences (P<0.05). Compared with group C, the expression of occludin and ZO-1 was increased in group PL, PM, and PH , and that of group PM, PH had a significant difference(P<0.05).Under the TEM ,we observed that the basement membrane of the blood-brain barrier of group S was uniform and integrity, but the ultrastructure of blood-brain barrier and hippocampal neurons of the four groups undergoing CPB had changed to some extent. Compared with group C and PL ,the ultrastructural changes of group PM, PH reduced significantly.The linear regression analysis indicated that there was significant relation between plasma level of S-100? protein and the expression of tight junction protein occluding and ZO-1 ,r is -0.9563 and-0.9737 respectively.Conclusion:1.Penehyclidine could reduce the inflammatory response of rats induced by CPB and had protective effects on cerebral injury induced by CPB.The middle and high dose of Penehyclidine had significantly role.2.Penehyclidine could protect the structure and function of neurons and blood-brain barrier, and had neuroprotective effect.3.Tight junction protein occludin and ZO-1 had correlation with the structure and function of blood-brain barrier.4.The plasma level of S-100? was one of the most important markers to detect cerebral injury, and could reflect the damage degree of blood-brain barrier.