Arc239

Male Sprague-Dawley rats (8–10 weeks old and 220–250 g) were purchased from the Medical Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Fifty-six rats were randomized into seven groups (n = 8 per group). Rats in the sham-operated group (S) did not undergo OALT. Rats in the model group (M) were intraperitoneally injected with saline 30 min before OALT. Rats in the D1 and D2 groups were intraperitoneally injected with 10 μg/kg (drug/body weight) and 50 μg/kg Dex (Hengrui Pharmaceutical Co., Ltd., Jiangsu, China) 30 min before OALT, respectively. Rats in the B1, B2, and B3 groups were intraperitoneally injected with 500 g/kg atipamezole (a nonspecific α_2A-AR siRNA blocker, Sigma-Aldrich, USA), 50 g/kg ARC239 (a specific α_2B/C-AR blocker, Santa Cruz Biotechnology, Inc., USA), and 1.5 mg/kg BRL-44408 (a specific α_2A-AR siRNA blocker, Sigma-Aldrich, USA) 40 min before receiving 50 μg/kg Dex prior to OALT, respectively. This study was performed with the approval of the Institutional Animal Care and Use Committee of Sun Yat-sen University in Guangzhou, China, and in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals.

Dexmedetomidine (Hengrui, Jiangsu, China), atipamezole (Sigma-Aldrich, USA), BRL44408 (Sigma-Aldrich, USA), and ARC239 (Santa Cruz, USA) were dissolved in 0.9% saline at 2.5 μg/ml, 25 μg/ml, 50 μg/ml and 2.5 μg/ml concentrations, respectively. Heparin (Chen Xin Pharmaceutical Co., Ltd., Shandong, China) was diluted in 0.9% saline or acetic acid Ringer’s solution at 25 U/ml; and 12.5 U/ml of protamine sulfate (KaiYue Pharmaceutical Co. Ltd., Beijing, China) was diluted in saline at 0.05% concentration.

Fifty-six rats weighing 220–280 g, fed by animal feed and raised in 25–27°C, were randomly divided into 7 groups with 8 rats/group. Sham-operated group (S) did not undergo I/R. Model group (M) was pretreated with normal saline by i.p. injection 30 min before operation. Rats in group D1 received 10 μg/kg Dex (Hengrui Pharmaceutical Co., Ltd., Jiangsu, China) by i.p. injection 30 min before operation. Rats in group D2 received 50 μg/kg Dex by i.p. injection 30 min before operation. Rats in groups B1, B2, and B3 received 500 μg/kg atipamezole (a nonspecific α₂ receptor blocker, Sigma-Aldrich, USA), 50 μg/kg ARC239 (a specific α_2B/c receptor blocker, Santa Cruz, USA), and 1.5 mg/kg BRL-44408 (a specific α_2A receptor blocker, Sigma-Aldrich, USA) by i.p. injection 40 min before receiving 50 μg/kg Dex prior to OALT.