Tukhovskaya Elena A, Shaykhutdinova Elvira R, Ismailova Alina M, Slashcheva Gulsara A, Prudchenko Igor A, Mikhaleva Inessa I, Khokhlova Oksana N, Murashev Arkady N, Ivanov Vadim T
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia.
Laboratory of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, Russia.
Biomedicines. 2021 Apr 9;9(4):407. doi: 10.3390/biomedicines9040407.
A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.
DSIP的一种结构类似物——肽KND，先前显示，与DSIP相比，在给予细胞毒性药物顺铂时具有更高的解毒功效。使用雄性SD大鼠急性心肌梗死模型和C57Bl/6小鼠急性局灶性中风模型对DSIP和KND进行了研究。与生理盐水处理的对照动物相比，KND处理的动物心肌梗死面积显著减小（19.1±7.3%对42.1±9.2%）。与对照生理盐水处理的动物相比，经鼻给予KND的动物脑梗死体积显著更低（7.4±3.5%对12.2±5.6%）。在心肌梗死和脑卒中小鼠模型再灌注的第一分钟注射KND可减少这些器官的梗死，这表明KND具有显著的心脏保护和神经保护作用，并且在再灌注期给药时，具有治疗心脏和脑部短暂性缺血发作后缺血-再灌注损伤的潜力。一项初步的预试验研究使用了在闭塞期间给予DSIP的心肌梗死模型，以及在闭塞期间给予KND的脑卒中小鼠模型，结果动物全部死亡。因此，对于心肌和脑的缺血-再灌注损伤，只有在再灌注期间才能使用这些肽。
