BTP2, a Store-Operated Calcium Channel Inhibitor, Attenuates Lung Ischemia-Reperfusion Injury in Rats.
Lung ischemia-reperfusion (I/R) injury is a critical complication following a lung transplant, cardiopulmonary bypass, pulmonary embolism, and trauma. Immune cells and their effector functions are involved in the lung I/R injury. Store-operated calcium channels (SOCC) are highly Ca2+-selective cation channels and have crucial effects on the immune system. It has been indicated that BTP2, a potent SOCC blocker, could inhibit pro-inflammatory cytokine production from immune cells both in vitro and in vivo. Therefore, this study was conducted to investigate the beneficial effects of BTP2 on lung I/R injury in Sprague-Dawley (SD) rats. The left lungs of male SD rats underwent ischemia for 60 min and reperfusion for 2 h. Treated animals received BTP2 4 mg/kg or 10 mg/kg intraperitoneally 30 min before the ischemia. The results revealed that pretreatment with BTP2 markedly attenuated I/R injury-induced pulmonary edema, microvascular protein leakage, neutrophil infiltration, adhesion molecules, cytokine production (e.g., ICAM-1, TNF-α, IL-1β, and IL-2), and the transcription factor nuclear factor of activated T cells c1 nuclear translocation in the lung tissue. These findings indicate that BTP2 can be a potential therapeutic drug for lung I/R injury and suggest that SOCC may play a critical role in lung I/R injury.
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wei
W
Zhang
Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Zeyou
Z
Qi
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. wangyaping5678@126.com.
Yaping
http://orcid.org/0000-0003-0504-3010
Y
Wang
D000813:Anilides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000517:prevention & control; D055370:Lung Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011292:Premedication / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D013830:Thiadiazoles / Q000494:pharmacology* / Q000627:therapeutic use
C476308:4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide; D000813:Anilides; D002121:Calcium Channel Blockers; D013830:Thiadiazoles
BTP2; inflammation; lung ischemia-reperfusion injury; store-operated calcium channels