허혈-재관류에 의한 신장조직 손상에서 Cobalt Chloride의 조직 보호작용에 관한 연구 = (The) Protective effect of cobalt chloride in experimental ischemia-reperfusion renal injury

다국어 초록 (Multilingual Abstract)

Brief ischemic periods before sustained ischemia known as ischemic preconditioning, have been shown to protect several organs, including the kidney, from ischemia-reperfusion( I-R ) injury. Cobalt chloride (COCL) has hypoxia-mimetic effects by inhibiting degradation of HIF-1α, which is a master regulator of genes activated by low oxygen tension. Herne oxygenase-1(HO-1), an inducible heat shock protein, is known to have cytoprotective effects against ischemic injury. This study evaluated the efficacy of COCL in a bilateral renal I-R injury model of male Sprague-Dawley rats. I-R renal injury was induced by 45 min clamping of both renal arteries. Rats in the sham(n=6) and I-R control groups(n=8) had been drinking tap water, whereas rats in the sham(n=6) and COCL treated I-R groups(n=9) had been drinking water containing 2 mM COCL from day -10 to day 1. The serum levels of creatinine, AST, LDH, and the renal tubular necrosis score based on light microscopic examination in each group were measured 24 hrs after surgery. The levels of renal gene expressions of HO-1, TGF-β, MCP-1, TNF-α, endeothelin-1, iNOS, Bcl-2 and Fas were measured by competitive RT-PCR. The serum level of creatinine 24 hrs after surgery was 2.6±1.1(mean±SD) mg/dL in I-R COCL treated group, significantly lower than that in I-R control group(4.8±1.6 mg/dL, p＜0.05). The tubular necrosis score of I-R COCL treated group was also significantly lower than that of I-R control group(p＜0.01). The renal gene expression of HO-1 was significantly upregulated in the COCL treated sham group compared to sham operated control rats. The HO-1 protein signal of kidney in the COCL treated I-R group measured by Western blot was also significantly higher than the level of I-R control group(p＜0.05). The expressions of TGF-β, MCP-1, TNF-α, endothelin-1 and Fas genes in the kidneys of COCL treated I-R rats were significantly lower than those of I-R control rats(all, p＜0.05). The level of Bcl-2 gene expression of kidneys in COCL treated I-R rats was significantly higher than the level of I-R control rats (p＜0.05).
In conclusion, it is speculated that the pretreatment of COCL in I-R injured rat model attenuates ischemic renal injury and at least in part, upregulation of renal HO-1 is involved in this mechanism.

목차 (Table of Contents)

• 목차
• Ⅰ. 서론 = 1
• Ⅱ. 대상 및 방법 = 3
• Ⅲ. 결과 = 8
• Ⅳ. 고찰 = 31
• Ⅴ. 결론 = 37
• 참고문헌 = 39
• ABSTRACT = 46