Mechanism of Traditional Tibetan Medicine Grubthobrildkr Alleviated Gastric Ulcer Induced by Acute Systemic Hypoxia in Rats

OBJECTIVE: This study was aimed at investigating the potential mechanism of Grubthobrildkr (GTB) on systemic hypoxia-induced gastric ulcers in rats and at detecting the chemical profile of GTB. METHODS: Male Sprague-Dawley rats were separated into control, hypoxia, hypoxia+omeprazole, and hypoxia+GTBs (0.25, 0.5, and 1.0 g·kg(−1)·d(−1)) groups. Systemic hypoxia was created in a hypobaric chamber to simulate 5000 m high altitude by adjusting the inner pressure and oxygen content for 6 days. After that, the ulcer index, pH, and volume of gastric juice were assessed. The levels of endothelin-1 (ET-1), gastrin (GAS), motilin (MTL), phospholipase A(2) (PLA(2)), and prostaglandin E(2) (PGE(2)) were detected by ELISA. The expression level of hydrogen potassium ATPase (H(+)-K(+)-ATPase), cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) was tested by western blotting. Chemical profile of GTB was revealed by UHPLC-Q-exactive hybrid quadrupole-orbitrap mass (UHPLC-Q-Orbitrap MS). RESULTS: GTB decreased the ulcer index in rats under hypoxia for six days, which was related to increased pH and volume of gastric juice, enhanced MTL and PGE(2) levels, and decreased ET-1 and PLA(2) levels of gastric mucosa. Furthermore, GTB decreased the level of H(+)-K(+)-ATPase and COX-2 while increased COX-1 levels in gastric mucosal tissue. 44 constituents were identified by UHPLC-Q-Orbitrap MS in GTB. CONCLUSION: GTB exerted a gastroprotective effect to alleviate gastric ulceration induced by acute systemic hypoxia in rats. The effect of GTB increasing the volume and pH of gastric juice in rats under acute systemic hypoxia could be regulated by gastrointestinal hormones, including MTL and ET-1. Mechanically, gastrointestinal protection of GTB was based on inhibition of the protons pumping H(+)-K(+)-ATPase and regulation of prostaglandin family in rats.