■缺血再灌注损伤(IRI)对医生提出了重大挑战,需要管理细胞损伤和保存器官功能。各种外科手术,比如四肢的血管手术,主动脉手术中腹主动脉的临时交叉夹紧,在四肢手术中使用止血带,可能诱发下肢IRI。糖尿病患者对IRI的易感性增加。本研究旨在研究富勒醇C60和七氟醚对下肢IRI模型小鼠肌肉组织的影响,并评估其预防链脲佐菌素诱导的糖尿病小鼠缺血再灌注并发症的潜力。
■将36只成年瑞士白化病小鼠随机分为6组,每组6只小鼠:对照组(C组),糖尿病组(D组),糖尿病缺血/再灌注组(DIR组),糖尿病缺血/再灌注富勒醇C60组(DIR-FC60组),糖尿病缺血/再灌注七氟醚组(DIR-S组),糖尿病-缺血/再灌注-七氟醚-富勒醇C60组(DIR-S-FC60)。链脲佐菌素(55mg/kg)腹腔给药以诱导相关组的糖尿病,在72小时时显示250mg/dL或更高的血糖水平的小鼠被认为是糖尿病。4周后,所有组均在麻醉下进行剖腹手术.在DIR-FC60和DIR-S-FC60组中,在缺血前30分钟腹膜内给予富勒醇C60(100mg/kg)。七氟醚,在100%氧气中以2.3%的速率和4升/分钟的速度输送,在缺血期间给予DIR-S和DIR-S-FC60组。在IR组中,在缺血期间,在肾下腹主动脉上放置微血管钳120分钟,然后取出夹钳和120分钟的再灌注期。再灌注结束时,取腓肠肌组织进行组织病理学和生化参数检查。
■组织病理学检查显示,与DIR组相比,DIR-S-FC60组的肌肉细胞解体和变性显着减少(p=0.041)。DIR-S中炎症细胞浸润明显较低,DIR-FC60和DIR-S-FC60组比DIR组(分别为p=0.031,p=0.011,和p=0.013)。DIR-FC60和DIR-S-FC60组的总损伤评分显著低于DIR组(分别为p=0.018和p=0.008)。此外,DIR-S中丙二醛(MDA)的水平,DIR-FC60和DIR-S-FC60组显著低于DIR组(分别为p<0.001、p<0.001和p<0.001)。过氧化氢酶(CAT)活性在DIR-S,DIR-FC60和DIR-S-FC60组高于DIR组(分别为p=0.001,p=0.014和p<0.001)。DIR-FC60和DIR-S-FC60组的超氧化物歧化酶(SOD)酶活性也高于DIR组(分别为p<0.001和p=0.001)。
■我们的发现表明,在糖尿病小鼠缺血前30分钟施用富勒醇C60,与七氟醚合用,在肌肉组织病理学中导致氧化应激的减少和IR相关损伤的纠正。我们认为,在IR之前施用富勒烯醇C60,再加上七氟醚在IR期间给药,对小鼠有保护作用。
UNASSIGNED: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes.
UNASSIGNED: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations.
UNASSIGNED: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively).
UNASSIGNED: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.