血红素氧合酶-1/一氧化碳系统在新生大鼠缺氧缺血性脑损伤中的作用

目的 观察新生大鼠缺氧缺血性脑损伤(HIBD)后血红素氧合酶-1/一氧化碳系统(HO-1/CO)变化,探讨其在HIBD中的作用.方法 7日龄Wistar新生大鼠按随机数字表法分为假手术组(Sham组)、缺氧缺血组(HIBD组)及HO抑制剂锌原卟啉组(Znpp组),每组6只.采用实时荧光定量PCR法、硫代巴比妥酸法(TBA法)、流式细胞术(FCM)和双波长定量测定法分别检测脑组织中HO-1 mRNA的表达、丙二醛(MDA)含量、脑组织细胞凋亡率及血中CO浓度.结果 与Sham组比较,HIBD组、Znpp组HO-1 mRNA表达均增强(分别为0.166±0.042、2.289±0.333、1.839±0.322),CO浓度升高分别为(0.460±0.009)%、(1.026±0.145)%、(0.735±0.079)%],差异有统计学意义(P＜0.05);但与HIBD组比较,Znpp组HO-1 mRNA表达明显减少,CO浓度降低,差异有统计学意义(P＜0.05).与Sham组比较,HIBD组、Znpp组MDA含量及细胞凋亡率均明显升高MDA含量分别为(1.016±0.210)nmol/mg prot、(1.945±0.312)nmol/mg prot、(3.202±0.693)nmol/mg prot,凋亡率分别为(0.108±0.009)%、(1.412±0.307)%、(2.458±0.565)%],差异有统计学意义(P＜0.05);与HIBD组比较,Znpp组MDA含量及细胞凋亡率明显增高,差异有统计学意义(P＜0.05).结论 缺氧缺血性脑损伤后HO-1/CO系统可能在脑损伤的恢复中起到一定的保护作用.

Role of heme oxygenase-1/carbon monoxide in hypoxic-ischemic brain damage in neonatal rats

Objective To observe the changes of brain heme oxygenase-1/carbon monoxide (HO-1/CO)in neonatal rats with hypoxic-ischemic brain damage(HIBD)injury and investigate the role of HO-1/CO in the recovery of HIBD. Methods Eighteen 7-day-old Wistar rats were randomly divided into sham-operated group,HIBDgroup and HIBDwith zinc protoporphyrin(ZnPP)treatment group (n=6).In the latter two groups,HIBD model was established by unilateral carotid ligation followed by timed exposure to 8%oxygen. Real-time fluorescent quantitative PCR Was performed to determine the expression of HO-1 mRNA and thiobarbituric acid(TBA)method was used to assay malondialdehyde (MDA)contentinthe braintissue of the rats.The cell apoptosis in the brain aRer HIBD was analyzed using flow cytometry,and the blood CO concentration was detected by the absorbance at 420mn and 432 nm.Results Compared to the sham-operated group.HO-1 mRNA expression and blood CO concentration were significantly increased in HIBD group and ZnPP group (P＜0.05).The rats with ZnPP group had significantly lower HO-1 mRNA expression and blood CO concentration than those in HIBD group(P＜0.05).HIBD resultedin significantly increased MDA content and cell apoptosis rate in the rat brain as compared to those in the sham-operated group(p＜0.05),and ZnPP treatment further increased the MDA content and cell apoptosis(P＜0.05). Conclusions Increased brain HO-1 mRNA expression and blood CO concentration in neonatal rats with HIBD are probably associated with the spontaneous recovery of neural tissue injury.