Mechanism of Salvia miltiorrhiza extract regulating Nrf2/ARE pathway in improving lung injury in rats with severe acute pancreatitis / 中国医师杂志

ABSTRACT

Objective:To investigate the mechanism of Salvia miltiorrhiza extract regulating nuclear factor-E2-related factor 2/antioxidant response element(Nrf2/ARE) pathway in improving lung injury in rats with severe acute pancreatitis (SAP).Methods:The SAP lung injury rat model was established by retrograde injection of 5% sodium taurocholate (1 ml/kg) into biliopancreatic duct. The rats were randomly divided into model group, Salvia miltiorrhiza extract (1.5 g/kg) group, ML385 (Nrf2/ARE pathway inhibitor, dose 20 mg/kg) group and Salvia miltiorrhiza extract + ML385 group (dose 1.5 g/kg, 20 mg/kg). The ascites volume was measured, and W/D ratio (W/D=wet weight/dry weight) was calculated. Pathological symptoms of lung tissues were detected by hematoxylin-eosin (HE) staining, and Holfbauer score was performed. Arterial blood gas indexes were detected by automatic blood gas analyzer. Serum superoxide dismutase (SOD), malonaldehyde (MDA) levels and lung reactive oxygen species (ROS) levels were detected by enzyme-linked immunosorbent assay (ELISA) kit. And the expression of Nrf2 protein was detected by Western blot.Results:Compared with the control group, the lung tissue of the model group showed obvious dilation and thickening of alveolar wall capillaries, enlargement of alveolar septum, hyperemia, edema and infiltration of inflammatory cells in the pulmonary interstitium. The ascites volume, ROS level in lung tissue, W/D and Holfbauer score, arterialpartial pressure of carbon dioxide (PaCO 2) and serum MDA levels were significantly increased ( P<0.05), while arterial partial pressure of oxygen (PaO 2), oxygenation index (OI) and serum SOD levels were significantly decreased ( P<0.05). Compared with the model group, the above pathological damage symptoms were alleviated in Salvia miltiorrhiza extract group, the ascites volume, ROS level of lung tissue, W/D, Holfbauer score, PaCO 2 and serum MDA level were decreased ( P<0.05); while the PaO 2, OI, serum SOD level and Nrf2 protein expression in lung tissue were increased ( P<0.05). Compared with the model group, the above pathological damage symptoms were aggravated in ML385 group, and the ascites volume, ROS level of lung tissue, W/D, Holfbauer score, PaCO 2 and serum MDA level were significantly increased ( P<0.05), while PaO 2, OI, serum SOD level, and Nrf2 protein expression in lung tissue were significantly decreased ( P<0.05). Compared with the Salvia miltiorrhiza extract group, the above pathological damage symptoms were aggravated in the Salvia miltiorrhiza extract + ML385 group; the ascites volume, ROS level in lung tissue, W/D, Holfbauer score, PaCO 2 and MDA level in serum were increased ( P<0.05), while PaO 2, OI, SOD level in serum and Nrf2 protein expression in lung tissue were decreased ( P<0.05). Conclusions:Salvia miltiorrhiza extract can protect lung tissue of rats with acute pancreatitis and lung injury by activating Nrf2/ARE signal.