Reparative role of dexmedetomidine in lung injury secondary to acute kidney injury

Abstract

Objective To investigate the reparative role of dexmedetomidine (Dex) in lung injury secondary to acute kidney injury (AKI). Methods A total of 75 healthy SPF male C57BL/6J mice (6-8 weeks old, weighing 20-22 g) were randomly divided into Sham group (standard laparotomy), renal ischemia reperfusion group (RIR, clamping of bilateral renal pedicles for 50 min followed by reperfusion), and Dex pretreatment group (Dex+RIR, intraperitoneal injection of 25 μg/kg Dex 15 min before bilateral renal pedicle clamping). Lung tissues, bronchoalveolar lavage fluid (BALF), and carotid arterial blood samples were collected from 5 mice in each group at 24, 48, 72, 96, and 120 h after modeling. Lung injury and repair, arterial blood partial pressure of oxygen (PaO2), and BALF contents of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were observed and detected for comparison in the groups at different time points. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the transcript levels of interleukin-6(IL-6) and lung surfactant protein C (SP-C). Results Within 48 h after AKI, lung injury score was increased and PaO2 was decreased in the RIR group and Dex+RIR group than the Sham group, but Dex pretreatment reversed the lung injury score and PaO2 level when compared with the RIR group. The lung injury score was still in a high level and PaO2 stayed low in the RIR group within 96 h after AKI, whereas the 2 indicators in the Dex+RIR group showed a sustained improvement in 48 h after injury. After AKI, the BALF contents of TGF-β1 and CTGF and mRNA level of IL-6 in lung tissue showed a decreasing trend from high level to low level in the RIR group, but all of them were significantly higher than those in the Sham group (P < 0.05), while Dex intervention resulted in an obvious decrease of TGF-β1 at 24-120 h (P < 0.01) and a notable reduction of IL-6 mRNA level at 24-72 h (P < 0.05), whereas a raising trend and maintenance of high level in CTGF at 48-96 h. After AKI, the mRNA level of SP-C in the RIR group were up-regulated at 24 h (P < 0.001, when compared to the Sham group) and then diminished to a low level at 48-120 h (P < 0.05, when compared to the RIR group at 24 h), however Dex pretreatment could alleviate the transcriptional repression of SP-C caused by AKI. Conclusion Dex can ameliorate pulmonary ventilation after lung injury secondary to AKI, and then advance the time for lung repair from 96-120 h to 48-72 h.

Keywords

• dexmedetomidine
• renal ischemia reperfusion
• acute lung injury
• repair