RESUMO
OBJECTIVE: To investigate whether herbal cake-separated moxibustion can activate nuclear factor erythroid 2-related factor 2 ï¼Nrf2ï¼ / antioxidant responsive element ï¼AREï¼ /hemeoxygenase-1 ï¼HO-1ï¼ signaling pathway to repair aspirin induced gastric mucosal injury ï¼GMIï¼ in rats. METHODS: SD rats ï¼half male and half femaleï¼ were randomly divided into blank control, model, moxibustion, inhibitor of HO-1 ï¼inhibitorï¼, model+inhibitor, moxibustion + inhibitor groups, with 20 rats in each group. The GMI model was established by gavage of aspirin 150 mg/kgï¼1 mL/100 gï¼. Herbal cake-separated moxibustion was alternatively applied to bilateral "Zusanli" ï¼ST36ï¼ and "Zhongwan" ï¼CV12ï¼ and bilateral "Pishu" ï¼BL20ï¼ and "Weishu" ï¼BL21ï¼ for 30 min, once daily for 8 days. The rats in the three inhibitor groups received intraperitoneal injection of HO-1 inhibitor zinc protoporphyrin ï¼5 mg/kgï¼. The rats' behavior score, emotional response score, skin hair score, diet score and stool state score were given. The GMI index was calculated according to Guth's methods. Histopathological changes of gastric mucosa were observed by H.E. staining. The activity of superoxide dismutase ï¼SODï¼ and the content of malondialdehyde ï¼MDAï¼ in the gastric mucosal tissue and serum were detected by ELISA. The levels of Nrf2/ARE/HO-1 signaling pathway-related factors Keap1, Nrf2, HO-1, CAT, GST, and NQO1 in the gastric mucosal tissue were detected by quantitative real-time PCR and Western blot, separately. RESULTS: Compared with the blank control group, the behavior score, emotional response score, skin hair score, diet score and stool state score, GMI index, MDA contents of gastric mucosal tissue and serum, expression le-vels of Keap1 mRNA and protein were significantly increased ï¼P<0.01ï¼, while the activity of gastric mucosal and serum SOD, the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins were considerably decreased ï¼P<0.01ï¼ in the model group. Compared with the model group, moxibustion obviously reversed the increase of emotional response score, skin hair score, stool state score, GMI index, MDA levels of gastric mucosal tissue and serum, and expression levels of Keap1 mRNA and protein ï¼P<0.01, P<0.05ï¼, and the decrease of activity of SOD of gastric mucosal and serum, and the expression levels of Nrf2, HO-1, CAT, GST and NQO1 mRNAs and proteins ï¼P<0.01, P<0.05ï¼. After administration of antagonist of HO-1, the effects of moxibustion were eliminated or weakened pronouncedly in reducing skin hair score, GMI index, contents of gastric mucosal and serum MDA, and expression of Keap1 mRNA and protein, and in up-regulating gastric mucosal and serum SOD, and expression of HO-1, CAT, GST and NQO1 mRNAs and proteins ï¼P<0.01, P<0.05ï¼. CONCLUSION: Herbal-cake separated moxibustion can improve the GMI in rats, which may be associated with its effects in reducing oxidative stress and activating Nrf2/ARE/HO-1 signaling pathway.