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        Streptozotocin - 당뇨병 백서에서 당뇨병 이환기간에 따른 대동맥의 이완능 저하 및 Oxygen - Free Radical 에 의한 이완능의 손상정도

        김정국(Jung Guk Kim),강승완(Sung Wan Kang),권삼(Sam Kwon),백운이(Woon Yi Back),김보완(Bo Wan Kim),하승우(Sung Woo Ha),서예경(Ye Kyung Seo),김수동(Su Dong Kim),김신우(Shin Woo Kim) 대한내과학회 1996 대한내과학회지 Vol.50 No.1

        N/A Objectives: Diabetes mellitus produces histological evidence of endothelial alterations as well as changes in vascular function in experimental animal. Oxygen free radicals interfere with or destroy endothelium-dependent relaxation in normal and diabetic blood vessels. The present study was investigated whether the duration of diabetic state can affect the severity of impairment in endothelium-dependent and/or independent relaxation and the sensitivity to oxygen free fadical (OFR)-induced damage in diabetic rat vasculature. Methods: The relaxative responses of aortic rings precontracted with norepinephrine in vitro to cumulative concentrations of acetylcholine (ACh) and nitroglycerine (NTG) were conducted in 3- and 10- week streptozotocin (STZ)-diabetic rats and agematched controls. After exposure to H2O2 generated by mixing xanthine and xanthine oxidase, the degree of impairment in relaxative responses to ACh and NTG were also compared between 3- and 10-week diabetic rats. Results: The relaxative responses of aortic rings produced by cumulative concentrations of ACh were significantly lower in both 3- and 10-week diabetic rats than in the age-matched controls. The impairments of relaxative responses to ACh in 10-week diabetic rats were significantly greater than those in 3-week ones. After H2O2 exposure, the impairments of relaxative responses to ACh in 3- and 10- week diabetic aortas was also significantly greater than those in the control ones. However, the severity of H -induced damage in 10-week diabetic aortas was not significantly different than that in 3-week ones. In contrast, aortic rings of 3- and 10-week diabetic rats could still be fully relaxed by NTG, even after exposure to H2O2. Conclusion: These findings suggest that in STZ-diabetic rat aortas selective impairment of endothelium-dependent relaxation to ACh can be found early even over a 3-week period after the induction of diabetes and the impairment may be greater in those with the longer duration of the diabetic state and that the impairment of the vascular relaxation by OFR is also selective to endothelium-dependent response but the sensitivity of OFR-induced damage may not be related to the duration of the diabetic state

      • Streptozotocin-당뇨병 백서에서 당뇨병 이환기간에 따른 대동맥의 이완능 저하 및 Oxygen-Free Radical에 의한 이완능의 손상정도

        김정국,김신우,김수동,서예경,하승우,김보완,백운이,권삼,강승완 경북대학교 병원 1997 경북대학교병원의학연구소논문집 Vol.1 No.1

        목적: 당뇨병의 이환기간이 혈관의 내피세포 의존성 및 비의존성 이완능의 저하에 미치는 영향과 이환기간에 따라 oxygen-free radical(OFR)에 의한 동맥이완능의 손상정도에 차이가 있는지를 알아보고자 하였다. 방법: Streptozotocin(STZ)으로 당뇨병이 유도된 3 주 및 10주째의 백서군과 연령이 비슷한 정상 대조백서군의 적출 대동맥환을 norepinephrine으로 수축시킨 상태에서 내피세포 의존성 이완제인 acetylcholine(ACh) 및 비의존성 이완제인 nitroglycerine(NTG)에 대한 이완능을 즉정하여 비교 관찬하였다. 또한 xanthine과 xanthine oxidase의 혼합으로 생성된 H₂O₂에 대동맥환을 노출시킨뒤 역시 ACh과 NTG에 대한 이완능의 손상정도를 비교하였다. 결과: 3주및 10주째 당뇨병 백서의 대동맥환은 모두 대조군 백서의 대동맥환에 비해 ACh에 대한 이완능이 유의하게 감소하였으며 10주째 당뇨병 백서군에서의 ACh에대한 이완능의 저하는 3 주째 당뇨병 백서군에 비해 유의하게 심하였다.H₂O₂에 노출시킨 뒤 ACh에대한 이완능은 3주 및 10주 째 당뇨병 백서군에서 모두 대조군에 비해 유의하게 심한 손상을 보였으나 3주와 10주째 당뇨병 백서군 사이의 손상정도의 차이가 통계학적으로 유의하지는 않았다. 한편 3주 및 10주째 당뇨병 백서군 모두 NTH에 대한 대동맥환의 이완능은 대조 백서군과 별다른 차이가 없었으며 또 H₂O₂에 노출시킨 뒤에도 NTG에 대한 이완능의 손상은 관찰되지 않았다. 결론: STZ-당뇨병백서에서 대동맥의 이완능은 당뇨병에 이환된지 3 주째에 이미 ACh에 대한 내피세포 의존성 이완능이 선택적으로 저하되며 당뇨병의 이환기간이 길수록 이완능의 저하가 심하였고, OFR에 의한 동맥 이완능의 손상도 내피세포 의존성 이완능에만 선택적으로 나타나나 이환기간에 따라 OFR에 의한 이완능 손상정도에는 뚜렷한 차이가 없음을 시사하고 있다. Objectives: Diabetes mellitus produces histological evidence of endothelial as well as changes in vascular function in experimental animal. Oxygen free radicals interfere with of destroy endothelium-dependent relaxation in normal and diabetic blood vessels. The present study was investigated whether the duration of diabetic state can affect the severity of impairment in endothelium-dependent and/or independent relaxation and the sensitivity to oxygen free fadical (OFR)-induced damage in diabetic rat vasculature. Methods: The relaxative responses of aortic ring precontracted with norepinephrine in vitro to cumulative concentrations of acetylcholine (ACh) and nitroglycerine (NTG) were conducted in 3- and 10- week streptozotocin (STZ)-diabetic rats and agematched controls. After exposure to H₂O₂generated by mixing xanthine and xanthine oxidase, the degree of impairment in relaxative responses to ACh and NTG were also compared between 3- and 10-week diabetic rats. Results: The relaxative responses of aortic rings produced by cumulative concentrations of ACh were significantly lower in both 3- and 10-week diabetic rats than in the age-matched controls. The impairments of relaxative responses to ACh in 10-week diabetic rats were significantly greater than those in 3-week ones. After H₂O₂ exposure, the impairments of relaxative responses to ACh in 3- and 10-week diabetic aortas was also significantly greater than those in the control in the control ones. However, the severity of H₂O₂-induced damage in 10-week diabetic aortas was not significantly different than that in 3-week ones. In contrast, aortic rings of 3- and 10-week diabetic rats could still be fully relaxed by NTG, even after exposure to H₂O₂. Conclusion: These findings suggest that in SRZ-diabetic rat aortas selective impairment of endothelium-dependent relaxation to Ach can be found early even over a 3-week period after the induction of diabetes and the impairment may be greater in those with the longer duration of the diabetic state and that the impairment of the vascular relaxation by OFR is also selective to endothelium-dependent response but the sensitivity of OFR-induced damage may not be related to the duration of the diabetic state.

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