Reduction of ischaemia-reperfusion injury in a rat lung transplantation model by low-concentration GV1001.
OBJECTIVE
Lung ischaemia-reperfusion (IR) injury is one of the major complications following lung transplantation. The novel peptide GV1001, which is derived from human telomerase reverse transcriptase, has been reported to possess both antitumour and anti-inflammatory effects. In this study, we focused on the anti-inflammatory effects of GV1001 to investigate the IR injury prevention effect of GV1001 in a rat lung transplantation model.


METHODS
An orthotopic left lung transplantation rat model was established using the modified cuff technique. We applied 50 ml of normal saline (control), Perfadex (low-potassium standard dextran containing perfusion solution), Perfadex with 5 mg GV1001 (5-mg GV, low concentration) and Perfadex with 50 mg GV1001 (50-mg GV, high concentration) as both flushing and preservation solutions. The left lung was stored in the same solution as the flushing solution at 4°C for 3 h. After transplantation, the recipient rats were monitored for 3 h. Arterial blood gas analysis (ABGA), bronchoalveolar lavage (BAL) analysis, wet/dry ratio, histological analysis, apoptotic cell analysis and cytokine [tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)] analysis were performed to determine the reduction or prevention effect of GV1001 regarding lung IR injury.


RESULTS
Compared with the control group, the neutrophil count in BAL, reperfusion oedema and cytokine (TNF-α, IL-6) levels of the transplanted lung were significantly decreased in the 5-mg GV group. Compared with the Perfadex group (16.85 ± 2.43), the neutrophil count in BAL was also significantly decreased in the 5-mg GV group (5.39 ± 0.81) (P< 0.001). In addition, the cytokine (TNF-α, IL-6) levels of the transplanted lung were also significantly decreased in the 5-mg GV group (41.99 ± 12.79, 1069.74 ± 98.48 pg/ml) compared with the Perfadex group (90.73 ± 23.87, 2051.92 ± 243.57 pg/ml) (P < 0.05 and P < 0.001, respectively). However, the 50-mg GV group showed less effect than the 5-mg GV group.


CONCLUSIONS
Adding a low concentration of GV1001 to the lung preservation solution (Perfadex) provided potential protective effects against IR injury after lung transplantation in rats. Therefore, GV1001 should be considered as a promising anti-inflammatory agent for IR injury.
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
Ji-Eun
JE
Chang
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
Hyun Jun
HJ
Kim
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
Eunjue
E
Yi
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sanghoon
S
Jheon
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea kmkim0070@snubh.org.|Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kwhanmien
K
Kim
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002245:Carbon Dioxide / Q000097:blood; D002951:Citrates; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007430:Intraoperative Care / Q000379:methods; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009504:Neutrophils; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019098:Telomerase / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002951:Citrates; D016207:Cytokines; D019188:Organ Preservation Solutions; D010446:Peptide Fragments; C070005:Perfadex; D002245:Carbon Dioxide; C514987:GV1001 peptide; D019098:Telomerase; D010100:Oxygen
Anti-inflammatory effect; Flushing solution; GV1001; Lung transplantation; Preservation solution