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两种保护剂对C离子诱导小鼠急性肝损伤的应答

Response of Two Protective Agents to Acute Injury Induced by 12C6+ Ions in Mouse Liver

    摘要
  • 摘要: 比较了N乙酰半胱氨酸（NAC）及乙酰左旋肉毒碱（ALCAR）对12C6+离子照射小鼠的损伤效应， 并探讨了其可能的作用机制。 利用4 Gy剂量的12C6+离子束对预先给予NAC（１00 mg/kg）和ALCAR（100 mg/kg）保护的昆明小鼠进行单次全身照射。 随后检测肝组织中总抗氧化能力(TAC)、 DNA单链断裂和细胞凋亡率。　结果显示， 与照射对照组相比， 提前给予NAC和ALCAR均极显著地增强了肝组织的抗氧化能力（P<0.001）， 减轻了12C6+离子导致的肝组织中DNA断裂（P<0.001）和细胞凋亡（P<0.001）。 此外， 还发现ALCAR组抗重离子辐照损伤的能力显著地高于NAC组（P<0.0５）。 实验结果提示了NAC和ALCAR可通过抵御组织内的氧化胁迫， 阻止DNA链的断裂和细胞的凋亡， 实现对C离子辐照损伤的保护效应。 而且ALCAR比NAC可能更适合成为有潜力、 有希望的抗C重离子辐射药物。 The present study was to evaluate the effect and mechanism of Nacetylcysteine(NAC) and AcetylLCarnitine hydrochloride(ALCAR) against 12C6+ ion beams on acute injury in the mouse liver. Pretreated with NAC (100 mg/kg) and ALCAR(100 mg/kg), KunMing mice were exposed to wholebody irradiation with the dose of 4 Gy. Mice were killed 2 h after irradiation, and then the liver tissues were quickly removed. TAC was measured by using chemical reagent kids, and DNAsingle strand breaks were determined by single cell gel electrophoresis, and the percentage of cell apoptosis were assayed by flow cytometry method. The results showed that NAC and ALCAR pretreatment significantly enhanced TAC(P<0.001), alleviated DNAsingle strand breaks(P<0.001) and cell apoptosis(P<0.001) of the liver tissues. Moreover, ALCARmediated radioprotection induced by 12C6+ ions is stronger than that of NAC (P<0.05). The data suggests that NAC and ALCAR both can ameliorate acute injury caused by 12C6+ ions in mice. In this study, NAC and ALCAR exert their radioprotective effect by virtue of resisting oxidative stress, enhancing TAC, alleviating DNAsingle strand breaks as well as cell apoptosis. Furthermore, the data imply that NAC and ALCAR may be suitable and promising as radioprotective drug against carbon heavy ions.

     

    Abstract: The present study was to evaluate the effect and mechanism of Nacetylcysteine(NAC) and AcetylLCarnitine hydrochloride(ALCAR) against 12C6+ ion beams on acute injury in the mouse liver. Pretreated with NAC (100 mg/kg) and ALCAR(100 mg/kg), KunMing mice were exposed to wholebody irradiation with the dose of 4 Gy. Mice were killed 2 h after irradiation, and then the liver tissues were quickly removed. TAC was measured by using chemical reagent kids, and DNAsingle strand breaks were determined by single cell gel electrophoresis, and the percentage of cell apoptosis were assayed by flow cytometry method. The results showed that NAC and ALCAR pretreatment significantly enhanced TAC(P<0.001), alleviated DNAsingle strand breaks(P<0.001) and cell apoptosis(P<0.001) of the liver tissues. Moreover, ALCARmediated radioprotection induced by 12C6+ ions is stronger than that of NAC (P<0.05). The data suggests that NAC and ALCAR both can ameliorate acute injury caused by 12C6+ ions in mice. In this study, NAC and ALCAR exert their radioprotective effect by virtue of resisting oxidative stress, enhancing TAC, alleviating DNAsingle strand breaks as well as cell apoptosis. Furthermore, the data imply that NAC and ALCAR may be suitable and promising as radioprotective drug against carbon heavy ions.

     

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