Objective To investigate the effects of breviscapine (Bre) on coronary artery injury in Kawasaki disease (KD) mice based on the Kelch-like epichlorohydrin related protein 1 (Keap1)/nuclear factor erythroid 2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Methods KD mice were constructed and randomly divided into the KD , the L-Bre, the M-Bre, the H-Bre groups (intraperitoneal injection of 20, 50, and 100 mg/kg of Bre), and the Bre + ML385 group (intraperitoneal injection of 100 mg/kg of Bre and 30 mg/kg Nrf2 inhibitor ML385). HE staining was applied to observe pathological changes in coronary artery tissue. TUNEL staining was used to observe apoptosis of artery tissue cells. ELISA was used to detect the expressions of cardiac injury factors in the blood [myoglobin (Mb), creatine kinase (CK), creatine kinase isoenzyme (CK-MB)], oxidative stress indicators [reactive oxygen species (ROS), superoxide dismutase (SOD)], and inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β)]. Western blot was applied to detect the expression of Keap1, Nrf2, HO-1, and NQO1 proteins in artery tissue. Results The Mb, CK, CK-MB, apoptosis rate, expression of TNF-α, IL-1β, ROS, and Keap1 in the KD group were higher than that in Control group, while the expression of SOD, Nrf2, HO-1 and NQO1 was lower than that in Control group (P<0.05). The Mb, CK, CK-MB, apoptosis rate, expression of TNF-α, IL-1β, ROS, and Keap1 in the L-Bre, M-Bre, and H-Bre groups were lower than that in KD group, while the expression of SOD, Nrf2, HO-1, and NQO1 was higher than that in KD group (P<0.05). The changes in the above indicators in the Bre+ML385 group were in the opposite direction compared to those in H-Bre group. Conclusions Bre can inhibit coronary artery injury in KD mice, which may be achieved by regulating the Keap1/Nrf2/ARE signaling pathway.
Key words
Kelch-like epichlorohydrin related protein 1 /
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Nuclear factor erythroid 2 related factor 2 /
Antioxidant response element /
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Breviscapine /
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Kawasaki disease /
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Coronary artery injury
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