| Objectives:Ischemia reperfusion (I/R) is a serious disease of the central nervous system. The mechanism of the injury has not yet fully understood and still lacks effective treatment.Biliverdin (BV), one of the catalytic products of heme oxygenase-1 (HO-1), has antioxidant and anti-inflammatory effect for many ischemia reperfusion injury events.In this study, biliverdin was used to treat for cerebral ischemia reperfusion injury (tMCAO) model rats to investigate the effect and mechanismof it on the cerebral ischemia reperfusion injury and influence on the expression of HO-1,at the same time, it can provide a theoretical basis for clinical treatment of cerebral ischemia reperfusion injury.Methods:1. The establishment of cerebral I/R injury model:rat models of cerebral I/R injury, that is transient middle cerebral artery occlusion (tMCAO) models were established according to the Zea-longa methods and the Zea-longa score was used to screen these animal models2. Animal grouping and drug intervention:Sixty-three adult male clean grade SD rats, weight 200-240g, were randomly divided into sham operation group (group S), only underwent the operation, but the middle cerebral artery was not occluded; cerebral ischemia reperfusion group (group C) and biliverdin group (group BV), cerebral ischemia caused by inserting a thread into the internal carotid artery to close up the origination of the middle cerebral artery in rats, pull out the thread and restore reperfusion after 2 h,2 ml of normal saline or biliverdin (35 mg/kg) intraperitoneal injection 15 min before,4 h after reperfusion and twice a day thereafter.3. Detection content and methods:NSS scores were evaluated from day 1 to day 5 after reperfusion; 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to determine the cerebral infarct volume 48 h after reperfusion; The expression levels of mRNA and protein of pro-inflammatory mediators tumor necrosis factor alpha (TNF-a), interleukin -6 (IL-6), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOs) and heme synthase-1 (HO-1) at the ischemic cerebral cortex were detected by fluorescence quantitative PCR (q-PCR) and Western blotting.Results:1. Compared with group S, the NSS score of group C was significantly increased, the difference was statistically significant (P<0.05); Compared with group C, the NSS score of group BV was slightly decreased, but there was no significant difference (P>0.05).2. Compared with group S, the cerebral hemisphere infarction volume of group C was significantly increased, the difference was statistically significant (P< 0.01); Compared with group C, the cerebral hemisphere infarction volume group BV was significantly reduced, the difference was statistically significant (P< 0.01).3. Compared with group S,the mRNA and protein expression levels of TNF-a, IL-6, IL-1β and iNOs of group C were significantly upregulated, the difference was statistically significant (P< 0.01); Compared with group C, the mRNA and protein expression levels of TNF-a, IL-6, IL-1βand iNOs of group BV were significantly downregulated, the difference was statistically significant (P< 0.01).4. Compared with group S, the mRNA and protein expression levels of HO-1 of group C were significantly upregulated, the difference was statistically significant (P<0.01); Compared with group C, the mRNA and protein expression levels of HO-1 of group BV were significantly downregulated, the difference was statistically significant (P<0.01).Conclusions:1. Biliverdin treatment can reduce cerebral infarction volume after cerebral ischemia reperfusion injury.2. Biliverdin has anti-inflammatory effect and treatment of biliverdin can reduce the expression of proinflammatory mediators in ischemic brain and thereby inhibit the inflammatory reaction and ameliorate the cerebral ischemic reperfusion injury.3. Treated with Biliverdin inhibit the expression of HO-1 by feedback regulation. |
PDF Full Text Request