Abstract:

PIM1 is a serine/threonine kinase that participates in the regulation of multiple signal pathways and plays an important role in many diseases. In order to explore the role of PIM1 kinase in cisplatin-induced acute kidney injury， C57BL/6 mice and renal tubular cells were selected as experimental objects. Cisplatin-induced acute kidney injury in mice was established by intraperitoneal injection of cisplatin. The levels of urea nitrogen and creatinine in serum were measured， renal pathology change was assayed by HE staining， qRT-PCR and Western blot were used to detect the expression levels of PIM1 mRNA and PIM1 protein. Renal tubular cells were infected by Adenovirus for overexpression of PIM1， the expression levels of p62、Beclin-1、LC3B were detected by Western blot， CCK-8 and flow cytometry were used to detect the renal tubular cell injury. Results showed that in vivo model， after injection of cisplatin， the levels of serum creatinine， urea nitrogen and tubular injury were significantly increased， the PIM1 mRNA and PIM1 protein expression in kidney tissues were dramatically increased. In vitro model， PIM1 mRNA and PIM1 protein expression levels significantly increased after Adenovirus infection. After cisplatin treated， the cell viability was decreased and the apoptosis was increased， while in the PIM1 overexpression group， the cell viability was increased and the apoptosis was decreased. After cisplatin treated， the expression level of p62 was decreased， the expression levels of Beclin-1， LC3B were increased， and autophagy was activated. Compared with the cisplatin treated group， the expression level of p62 was increased， the expression levels of Beclin-1， LC3B were decreased， and autophagy was weakened in the PIM1 overexpression group. In conclusion， PIM1 was activated in cisplatin-induced acute kidney injury， overexpression of PIM1 alleviated the cisplatin-induced renal tubular cells injury by inhibiting excessive autophagy.

Key words: PIM1 kinase, acute kidney injury, cisplatin, autophagy

摘要：

PIM1是一种丝氨酸/苏氨酸激酶，参与多种信号通路调控，在许多疾病中发挥重要作用。为了探讨PIM1激酶在顺铂诱导的急性肾损伤中的表达情况及其作用，选取C57BL/6小鼠和肾小管细胞作为实验对象。采用腹腔注射顺铂构建顺铂诱导的急性肾损伤小鼠模型，通过检测肌酐尿素氮水平，HE染色检测肾组织病理变化，qRT-PCR和Western blot检测肾组织PIM1 mRNA和蛋白表达水平。腺病毒感染肾小管细胞构建PIM1过表达顺铂损伤模型，qRT-PCR和Western blot检测p62、Beclin-1和LC3B的表达水平，CCK-8以及流式细胞术评价肾小管细胞损伤情况。结果表明，在小鼠模型中，腹腔注射顺铂后血清肌酐和尿素氮水平显著升高，小鼠肾脏组织病理呈急性肾小管坏死状，肾组织中PIM1 mRNA与PIM1蛋白表达水平显著升高。在肾小管细胞模型中，PIM1过表达处理后，PIM1 mRNA及PIM1蛋白水平显著升高；顺铂处理后，肾小管细胞活性下降、细胞凋亡增加，过表达PIM1顺铂处理组较单纯顺铂处理组细胞活性增高，细胞凋亡率降低，细胞损伤减轻。顺铂处理后，肾小管细胞中p62蛋白表达减少，Beclin-1、LC3B蛋白表达增加，自噬激活；过表达PIM1顺铂处理组较单一顺铂处理组细胞p62蛋白表达增加，Beclin-1、LC3B蛋白表达减少，自噬减弱。研究结果说明，PIM1在Cis-AKI模型中被激活，过表达PIM1可以减轻顺铂导致的肾小管细胞损伤，这可能与其抑制细胞过度自噬有关。

关键词: PIM1激酶, 急性肾损伤, 顺铂, 自噬