Oliveira Caroline Assunção, Mercês Érika Azenathe Barros, Portela Fernanda Santos, De Benedictis Júlia Mafra, De Benedictis Laís Mafra, da Silva Antônio Victor Brito, Campanati João de Assis Gonçalves, de Melo Fabrício Freire, Oliveira Márcio Vasconcelos, de Magalhães Amélia Cristina Mendes, Soares Telma de Jesus, Amaral Liliany Souza de Brito
Instituto Multidisciplinar em Saúde, Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal da Bahia, Vitória da Conquista, Rua Rio de Contas, 58, Candeias, 45029-094, Bahia, Brazil.
Apoptosis. 2023 Apr;28(3-4):566-575. doi: 10.1007/s10495-023-01816-6. Epub 2023 Jan 19.
Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.
凋亡信号通路参与了抗肿瘤药物顺铂（Cis）诱导的急性肾损伤（AKI）。已知机械应激会增加白细胞介素（IL）-11，这是一种具有抗凋亡和抗坏死作用的多效细胞因子。我们比较了高强度间歇训练（HIIT）与低强度持续训练（LICT）和中等强度持续训练（MICT）对顺铂诱导的肾毒性雌性大鼠肾脏中IL-11水平及凋亡标志物表达的影响。为此，将动物分为五组（n = 7）：对照组和久坐组（C + S）；顺铂组和久坐组（Cis + S）；顺铂组和低强度持续训练组（Cis + LICT）；顺铂组和中等强度持续训练组（Cis + MICT）；顺铂组和高强度间歇训练组（Cis + HIIT）。在跑步机跑步8周结束时，大鼠单次注射顺铂（5 mg/kg），7天后对其实施安乐死。收集血清和肾脏样本以评估血尿素氮（BUN）、肿瘤坏死因子受体1（TNFR1）和2（TNFR2）、半胱天冬酶-3、（p38）丝裂原活化蛋白激酶（MAPK14）、p53、Bax、Bak、Bcl-2和Bcl-xL的基因表达，肾脏中IL-11、IL-8和p53的水平，以及肾组织中裂解的半胱天冬酶-3、Bax, Bcl-2和（p38）MAPK的免疫定位。我们的数据表明，所有训练组肾脏中IL-11水平均呈现显著的强度依赖性增加，同时促凋亡标志物的局部表达减少，抗凋亡标志物增加，但这些效应在高强度间歇训练组中更为明显。因此，高强度间歇训练似乎比传统的持续训练通过调节凋亡信号通路能提供更好的肾脏保护作用，且这种作用可能与肾脏中IL-11水平的升高有关。
