胆红素的抗氧化作用及血红素加氧酶对胆红素的调控作用

目的在间二硝基苯(m-DNB)诱导的大鼠氧化损伤的基础上,观察胆红素、血红素加氧酶的变化,并分析两者在抗氧化方面的作用和意义。方法用5,10,20 mg/kg的m-DNB染毒大鼠后,分别于2周和4周测定大鼠血清胆红素(bilirubin,BR)含量及肝脏微粒体血红素加氧酶(heme oxygenase,HO)活力及血清GSSG/GSH比值。另用一定量的m-DNB加锌卟啉(ZnPP)或血红素(heme)染毒,1周后测定大鼠血清BR含量、HO活力和GSSG/GSH比值。结果染毒2周时,各染毒组BR含量和HO活力均明显上升,且与m-DNB剂量呈显著正相关(P<0.01),染毒4周时,BR含量明显降低,仅在高剂量组仍高于对照组,低、中剂量组回落至正常水平,但与m-DNB仍呈显著相关(P<0.01);HO活力在低、中剂量组进一步升高,而高剂量组回落至正常水平。同时,m-DNB ZnPP组和m-DNB heme组HO活力显著低于对照组和m-DNB染毒组(P<0.05),BR水平高于对照组而低于m-DNB染毒组(P<0.05),GSSG/GSH比值高于对照组和m-DNB染毒组(P<0.05)。结论BR和HO两者均具有抗氧化作用,提示,HO在机体氧化应激时对胆红素可能具有双相调控作用。

Antioxidation of Bilirubin and Regulation of Heme Oxygenase in Bilirubin

Objective To observe the changes of serum bilirubin(BR)and liver heme oxygenase(HO)after inducing oxidation injury in rats by m-dinitrobenzene(m-DNB)and to analyze their effects and significance in anti-oxidation.Methods Rats were exposed to 5,10,and 20 mg/kg m-DNB.BR contents,GSSG/GSH ratios and microsome HO activities were measured after 2 and 4 weeks' exposure.On the other hand,certain amount of m-DNB ZnPP or heme was used for exposure,after one week BR,HO activities and GSSG/GSH ratios in rats were measured.Results When exposed for two weeks,BR and HO activities in all exposed groups increased significantly showing positive correlation with the m-DNB dosages(P<0.01).When exposed for 4 weeks,BR lowered significantly.Only the content in high dosage group was still higher than that of the control,while those in low and medium dosage groups lowered to normal levels;however,they still significantly correlated with m-DNB.The activities of HO in low and medium dosage groups further increased,while that in high dosage group lowered to normal level.HO activities in m-DNB ZnPP group and m-DNB heme group were significantly lower than those of the control and m-DNB exposed groups(P<0.05).BR contents were higher than the control and lower than that of m-DNB group(P<0.01).The ratios of GSSG/GSH were higher than those of the control and m-DNB exposed groups(P<0.05).Conclusions Both BR and HO show anti-oxidation effects which suggest that HO might show dual-directional adjusting effect on BR anti-oxidation.