CAJ | 학술논문

本实验研究内源性血红素氧化酶(heme oxygenase,HO)/一氧化碳(CO)系统在大鼠高血压发病中的作用.2,4-二甘油次卟啉锌(ZnDPBG)是体内HO活性抑制剂.用ZnDPBG处理大鼠后,检测其血压和血浆肾上腺素、去甲肾上腺素、内皮素、硝酸盐和亚硝酸盐、6-酮-PGF1α的改变,同时测定主动脉平滑肌中HO活性和CO的生成.此外还观察了CO和HO底物血红素-左旋赖氨酸盐(heme-L-lysinate,HLL)对HO抑制性大鼠和自发性高血压大鼠血压的影响.结果发现:ZnDPBG使大鼠血浆肾上腺素、去甲肾上腺素、内皮素和一氧化氮代谢产物含量明显增加,同时动脉血压升高;主动脉平滑肌HO活性和CO产生明显受到抑制.CO能使HO抑制性大鼠平均动脉压(MABP)明显降低,HLL则无此效应.在高血压大鼠,CO或HLL均能导致其MABP急性降低.本实验提示HO/CO系统在体内有抗高血压生物学效应,内源性CO在血管张力调节和高血压发生的机制中具有重要作用.
본실험연구내원성혈홍소양화매(heme oxygenase,HO)/일양화탄(CO)계통재대서고혈압발병중적작용.2,4-이감유차계람자(ZnDPBG)시체내HO활성억제제.용ZnDPBG처리대서후,검측기혈압화혈장신상선소、거갑신상선소、내피소、초산염화아초산염、6-동-PGF1α적개변,동시측정주동맥평활기중HO활성화CO적생성.차외환관찰료CO화HO저물혈홍소-좌선뢰안산염(heme-L-lysinate,HLL)대HO억제성대서화자발성고혈압대서혈압적영향.결과발현:ZnDPBG사대서혈장신상선소、거갑신상선소、내피소화일양화담대사산물함량명현증가,동시동맥혈압승고;주동맥평활기HO활성화CO산생명현수도억제.CO능사HO억제성대서평균동맥압(MABP)명현강저,HLL칙무차효응.재고혈압대서,CO혹HLL균능도치기MABP급성강저.본실험제시HO/CO계통재체내유항고혈압생물학효응,내원성CO재혈관장력조절화고혈압발생적궤제중구유중요작용.
The present study investigated the contribution of endogenous heme oxygenase (HO)/carbon monoxide (CO) system to hypertension pathogenesis of rats. Zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG),an inhibitor of heme oxygenase (HO), was used to inhibit HO activity in vivo. It was found that the blood pressure of rats with HO inhibition was significantly elevated, and plasma levels of adrenaline, noradrenaline,endothelin, nitrate and nitrite were significantly increased. HO activity and HbCO formation within vascular smooth muscle tissues were significantly inhibited after administration of ZnDPBG. Furthermore, administration of exogenous CO into HO inhibiting rats led to MABP decrease, but injection of HO substrate, heme-Llysinate, had no effect on HO inhibition-induced hypertension. In spontaneously hypertensive rats, injection of exogenous CO resulted in a significant decrease of MABP, and heme-L-lystnate had a similar effect with exogenous CO. These data show that HO/CO system has an anti-hypertension biological action, suggesting that endogenous CO plays an important role in hypertension pathogenesis.