AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondri...AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS： Wistar rats were divided into three groups： Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment （2 μg/1O0 g bw/d）. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS： Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential （in status 4 and 3）; an increase of intramitochondrial reactive oxigen species （ROS） generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION： These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.展开更多
基金Supported by The Spanish Program I + D, SAF 2005/08113
文摘AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS： Wistar rats were divided into three groups： Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment （2 μg/1O0 g bw/d）. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS： Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential （in status 4 and 3）; an increase of intramitochondrial reactive oxigen species （ROS） generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION： These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.
文摘本实验旨在分析绿豆皮多糖(mung bean skin polysaccharide,MBSP)的结构表征和抗氧化活性.结果表明:MBSP是一种相对分子量362.66kD、单糖组成及摩尔比为阿拉伯糖:半乳糖:半乳糖醛酸:木糖:葡萄糖=28.45∶4.67∶3.29∶1.51∶1.00的酸性多糖;红外光谱结果显示存在多糖特征吸收峰,扫描电镜等结果显示其表面光滑且呈片状分布,是一种热稳定性较弱的半晶型聚合物;平均粒径(107.0±3.4)nm、Zeta电位(—11.6±0.11)mV;流变学分析结果显示MBSP溶液体系倾向于形成弱凝胶结构.体外抗氧化活性研究结果表明,MBSP具有良好的1,1G二苯基G2G三硝基苯肼(doctoral programs in publichealth,DPPH)自由基和2,2G连氮基—双G(3G乙基苯并二氢噻唑啉G6G磺酸)(agreement on basic telecommunicationservices,ABTS)自由基清除能力.此外,H2O2诱导的大鼠肠上皮细胞(IECG6细胞)的氧化损伤研究结果表明:MBSP能够显著提高氧化损伤细胞的存活率,有效提高超氧化物歧化酶(superoxidedismutase,SOD)的活力和降低丙二醛(malondialdehyde,MDA)含量,具有明显的氧化损伤保护作用,为MBSP的开发和利用提供了一定的理论基础.
