胰岛素抵抗状态下血红素氧合酶-1/一氧化碳与一氧化氮合酶/一氧化氮相互调节的研究

Interaction between hemeoxygenase-1/carbon monoxide and nitricoxide synthase/nitrogen monoxide in insulin resistance states.

目的探讨胰岛素抵抗状态下血红素氧合酶-1(HO-1)/一氧化碳(CO)与一氧化氮合酶(NOS)/一氧化氮(NO)的相互调节关系。方法通过6周高脂饮食成功复制胰岛素抵抗SD大鼠模型44只。分为胰岛素抵抗组26只,正铁血红素组10只,锌原卟啉组8只;分别腹腔注射生理盐水、正铁血红素、锌原卟啉。12只经6周普通饲料喂养的SD大鼠为对照组,给予腹腔注射生理盐水。检测血CO含量以及胸主动脉组织的NO、诱导型NOS(iNOS)、内皮型NOS(eNOS)的水平,RT-PCR检测主动脉iNOS、eNOS mRNA的表达。结果正铁血红素提高胰岛素抵抗大鼠主动脉组织eNOS活性及其mRNA表达,降低iNOS活性及其mRNA表达,降低血清及动脉组织的NO水平,增加动脉血CO水平。结论HO-1通过对NOS/NO信息通道的调节,抑制iNOS的活性,从而使应激状态下NO水平下降,发挥HO-1的血管保护作用。

Objective To investigate the interaction between heine oxygenase-1 （HO-1）/ carbon monoxide （CO） and nitricoxide synthase （NOS）/ nitrogen monoxide （NO） in insulin resistance states（IR）. Methods IR model of Sprague- Dawley（ SD ） rats was successfully established by feeding with high fat diet （ HFD） for 6 weeks. Then the model rats were randomly divided into 2 subgroups, namely hemin group（n = 10） and zinc protoporphyrin-IX （ ZnPP） group（ n =8） as well as Control group（ n = 12） ,and were treated every other day with abdominal injections of hemin or ZnPP-IX for 4 weeks. Blood carbon momxide （ CO） contents,the levels of NO, iNOS, eNOS in thoracic aorta were assessed. The expressions of mRNA of iNOS and eNOS were detected by reverse transcription-polymerase chain reaction （ RT-PCR ）. Results Hemin could enhance the eNOS activity and the expression of eNOS mRNA in aortas, and inhibitiion of the iNOS activity and the expression of iNOS mRNA, decrease the NO level in serum and in aortas, and increase the contents of serum CO. Conclusion The protective effect of HO-1 against vascular injury is due to the regulation of NOS/NO and inhibition of the iNOS activity, thus the NO level is decreased in insulin resistance states.