원거리 허혈양상화가 흰쥐의 간에서 HO-1과 HSP70, iNOS 발현에 미치는 영향
Changes in HO-1, HSP70 and iNOS Expressions in the Rat Liver after Remote Ischemic Preconditioning
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허혈양상화는 허혈 전에 짧은 허혈과 재관류를 반복하는 방법으로 장시간의 허혈 및 재관류 손상으로부터 조직을 보호하는데 효과적이다. 이에 저자들은 흰쥐의 다리에서 원거리 허혈양상화를 실시한 후,간에서 발현되는 HO-1, HSP70, iNOS 단백질의 변화를 알아보고자 본 실험을 실시하였다. 허혈양상화 처치는 35주령 된 흰쥐의 왼온엉덩동맥에서 5분 허혈과 5분 재관류를 3회와 10회 반복하여실시하였다. 허혈양상화 후 재관류 0, 3, 6, 24, 72시간에 간에서 발현되는 HO-1, HSP70, iNOS 단백질의 변화는 면역조직화학염색과 Western blot 분석을 이용하여 알아보았고, 다음과 같은 결과를 얻었다. 간에서 HO-1 발현은 허혈양상화 3회군과 10회군에서 재관류 72시간에 정상대조군보다 유의성 있게 증가하였다. HSP70 발현은 허혈양상화 3회군에서 재관류 6시간에 정상대조군보다 증가하였고, 재관류 72시간에는 정상대조군과 비슷하였다. 그리고 허혈양상화 10회군에서 HSP70 발현은 재관류 직후에 정상대조군보다증가하였고, 재관류 24시간과 72시간에는 정상대조군보다 유의성 있게 감소하였다. iNOS 발현은 허혈양상화3회군과 10회군에서 재관류 24시간에 정상대조군보다 유의성 있게 증가하였으나, 재관류 72시간에는 감소하였다. 본 실험결과를 종합해보면, 흰쥐의 왼온엉덩동맥에서 짧은 허혈과 재관류를 반복 실행하면, 간에서 재관류초기에는 HSP70 발현이 증가하고, 재관류 72시간에는 HO-1 발현이 증가하며, iNOS 발현은 감소하는 것을알 수 있었다.
Abstract
Ischemic preconditioning (IP), short pre-treatment sublethal ischemia, induces a state of protection against subsequent prolonged ischemia-reperfusion. The purpose of this study was to investigate the expression of HO-1, HSP70, and iNOS proteins in the liver subjected to the courses of reperfusion after repetitive cycles of remote IP in the rat. Using thirty five week-old rats, the remote preconditioning was undertaken by vascular clamp occlusion of blood flow to one hindlimb, with 3 and 10 cycles of 5 minutes occlusion followed by 5 minutes reperfusion. The liver was removed 0, 3, 6, 24, and 72 hours of reperfusion after remote IP and assayed by immunohistochemical staining and Western blotting analyses for anti-HO-1, anti-HSP70, and anti-iNOS antibodies. The expression of HO-1 in rat liver increased at 72 hours of reperfusion groups after 3 and 10 cycles of remote IP, compared with normal control groups. The expression of HSP70 in rat liver increased at 6 hours of reperfusion groups after 3 cycles of remote IP, compared with normal control groups. The expression of HSP70 in rat liver increased at 0 hour of reperfusion groups after 10 cycles of remote IP, compared with normal control groups and decreased at 24 and 72 hours of reperfusion groups. The expression of iNOS in rat liver increased at 24 hours of reperfusion groups, but decreased at 72 hours of reperfusion groups after 3 and 10 cycles of remote IP, compared with normal control groups. In summary, these results showed that at early phase of reperfusion after remote IP, HSP70 expression was increased in rat liver. However, at 72 hrs of reperfusion after remote IP, HO-1 expression was increased and iNOS expression was decreased in rat liver.
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