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Abstract：
OBJECTIVE: To investigate the effect of bradykinin (BK) on cisplatin (DDP)-induced cardiotoxicity at the cellular level and its cytological mechanism.
METHODS: The toxic effects of DDP on GP-H1 cells, and the effects of BK on DDP cardiomyocyte survival rate, DDP-induced malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), reactive oxygen species (ROS), mitochondria membrane potential (MMP) and apoptosis were explored.
RESULTS: DDP at different concentrations inhibited GP-H1 cells at 12 h after administration, and the inhibitory effect was more prominent at 24 h after administration and continued until 72 h after administration. The severity of GP-H1 cell damage induced by DDP was reduced by 0.1 μM, 1 μM, and 10 μM BK. After GP-H1 cells were treated with DDP, ROS levels increased and MMP levels decreased, while BK intervention inhibited these effects. At 24 h after DDP treatment, Bax/bcl-2 increased in GP-H1 cells, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. After intervention with BK, it was shown that Bax/Bcl-2 was significantly reduced, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. Bax/Bcl-2 and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 of GP-H1 cells were basically not affected by BK alone.
CONCLUSIONS: The protective effect of BK on DDP-induced GP-H1 cell damage in guinea pig is related to the activation of PI3K/Akt/NO signaling pathway by BK, which reduces oxidative stress levels in cardiomyocytes and also acts as an anti-apoptotic agent.
METHODS: The toxic effects of DDP on GP-H1 cells, and the effects of BK on DDP cardiomyocyte survival rate, DDP-induced malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), reactive oxygen species (ROS), mitochondria membrane potential (MMP) and apoptosis were explored.
RESULTS: DDP at different concentrations inhibited GP-H1 cells at 12 h after administration, and the inhibitory effect was more prominent at 24 h after administration and continued until 72 h after administration. The severity of GP-H1 cell damage induced by DDP was reduced by 0.1 μM, 1 μM, and 10 μM BK. After GP-H1 cells were treated with DDP, ROS levels increased and MMP levels decreased, while BK intervention inhibited these effects. At 24 h after DDP treatment, Bax/bcl-2 increased in GP-H1 cells, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. After intervention with BK, it was shown that Bax/Bcl-2 was significantly reduced, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. Bax/Bcl-2 and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 of GP-H1 cells were basically not affected by BK alone.
CONCLUSIONS: The protective effect of BK on DDP-induced GP-H1 cell damage in guinea pig is related to the activation of PI3K/Akt/NO signaling pathway by BK, which reduces oxidative stress levels in cardiomyocytes and also acts as an anti-apoptotic agent.
摘要：
目的：从细胞水平探讨缓激肽(BK)对顺铂(DDP)心脏毒性的影响及其细胞学机制。
方法：DDP对GP-H1细胞的毒性作用，以及BK对DDP心肌细胞存活率的影响，DDP诱导的丙二醛（MDA），乳酸脱氢酶（LDH），超氧化物歧化酶（SOD），活性氧（ROS），探讨线粒体膜电位（MMP）和细胞凋亡。
结果：不同浓度的DDP在给药后12小时抑制GP-H1细胞，抑制作用在给药后24h更为突出，并持续到给药后72h。DDP诱导的GP-H1细胞损伤的严重程度降低0.1μM，1μM,和10μMBK。用DDP处理GP-H1细胞后，ROS水平升高，MMP水平降低，而BK干预抑制了这些作用。DDP治疗后24小时，Bax/bcl-2在GP-H1细胞中增加,Caspase-3、p-NF-κB的表达,p-p38和p-Smad2下降。BK干预后,结果显示Bax/Bcl-2显著降低,Caspase-3、p-NF-κB的表达,p-p38和p-Smad2下降。Bax/Bcl-2和Caspase-3、p-NF-κB的表达,GP-H1细胞的p-p38和p-Smad2基本上不受单独BK的影响。
结论：BK对DDP诱导的豚鼠GP-H1细胞损伤的保护作用与BK激活PI3K/Akt/NO信号通路有关。其降低心肌细胞中的氧化应激水平并且还充当抗凋亡剂。
方法：DDP对GP-H1细胞的毒性作用，以及BK对DDP心肌细胞存活率的影响，DDP诱导的丙二醛（MDA），乳酸脱氢酶（LDH），超氧化物歧化酶（SOD），活性氧（ROS），探讨线粒体膜电位（MMP）和细胞凋亡。
结果：不同浓度的DDP在给药后12小时抑制GP-H1细胞，抑制作用在给药后24h更为突出，并持续到给药后72h。DDP诱导的GP-H1细胞损伤的严重程度降低0.1μM，1μM,和10μMBK。用DDP处理GP-H1细胞后，ROS水平升高，MMP水平降低，而BK干预抑制了这些作用。DDP治疗后24小时，Bax/bcl-2在GP-H1细胞中增加,Caspase-3、p-NF-κB的表达,p-p38和p-Smad2下降。BK干预后,结果显示Bax/Bcl-2显著降低,Caspase-3、p-NF-κB的表达,p-p38和p-Smad2下降。Bax/Bcl-2和Caspase-3、p-NF-κB的表达,GP-H1细胞的p-p38和p-Smad2基本上不受单独BK的影响。
结论：BK对DDP诱导的豚鼠GP-H1细胞损伤的保护作用与BK激活PI3K/Akt/NO信号通路有关。其降低心肌细胞中的氧化应激水平并且还充当抗凋亡剂。
