RESUMO
Objective To investigate the effects of glucagon like peptide 1 (GLP-1) agonist on myocardial hypoxia reoxygenation injury and its molecular mechanism. Methods H9C2 cells were divided into control group, hypoxia reoxygenation(H/ R) group, H/ R+GLP-1 group, and H/ R+GLP-1+phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 group. The cell proliferation activity, apoptosis rate, enzyme contents in the medium and the expressions of apoptosis-related genes were detected. After animal model of myocardial ischemia reperfusion injury (I/ R) was established and was treated with GLP-1 agonist and PI3K inhibitor, serum enzyme contents were detected. Results Hypoxia reoxygenation decreased the myocardial cell proliferation activity and phosphorylated-PI3K(p-PI3K), phosphorylated-protein kinase B (p-Akt), Bcl-2 protein expressions, increased the apoptotic cell number and creatine kinase ( CK), creatine kinase-MB ( CK-MB), lactate dehydrogenase ( LDH) contents in cell culture medium and Bax, caspase-3 protein expressions, which were ameliorated by GLP-1 ( all P < 0. 05). The myocardial cell proliferation activity and Bcl-2 protein expression of H/ R+GLP-1+LY294002 group were significantly lower than those of H/ R+GLP-1 group while the apoptotic cell number and CK, CK-MB, LDH contents in cell culture medium and Bax, Caspase-3 protein expressions were significantly higher (all P<0. 05). Serum CK, CK-MB, and LDH contents in rats of I/ R group were significantly higher than those in control group and I/ R+GLP-1 group. Serum CK, CK-MB, and LDH contents in rats of I/ R+GLP-1+LY294002 group were significantly higher than those in I/ R+GLP-1 group(all P < 0. 05). Conclusion GLP-1 agonist is able to protect the myocardial hypoxia reoxygenation injury via activating PI3K/ Akt signaling pathway.
RESUMO
To study the effect of glucagon-likepeptide 1(GLP-1)receptor agonist on insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease. 36 male SD rats were served as the experimental animal and randomly divided into control group, model group, and GLP-1 group. The rats of control group were given routine diet with intraperitoneal injection of normal saline, those in model group were given high fat diet and intraperitoneal injection of normal saline, while GLP-1 group rats were fed with high fat diet and intraperitoneal injection of liraglutide. After 4 weeks of treatment, insulin resistance, lipid metabolism, liver injury and oxidative stress were all assessed. Serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, alanine transaminase(ALT), aspartate transaminase(AST)levels and total cholesterol, triglyceride contents in liver tissue, and as well as homeostasis model assessment for insulin resistance(HOMA-IR)levels of model group were significantly higher than those of control group, complex insulin sensitivity index(ISIcomp)level was significantly lower than that of control group; serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, ALT, AST contents and HOMA-IR levels of GLP-1 group were significantly lower than those of model group, ISIcomp level was significantly higher than that of model group; superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), catalase(CAT)contents in liver tissue of model group were significantly lower, while malondialdehyde content and SOD, GSH-Px, CAT, NF-E2 related factor-2(Nrf-2), antioxidant response element(ARE), heme oxygenase-1(HO-1), quinone oxidoreductase-1(NQO-1), glutathione thiol transferase(GST)mRNA expression were significantly higher than control group; SOD, GSH-Px, CAT contents and SOD, GSH-Px, CAT, Nrf-2, ARE, HO-1, NQO-1, GST mRNA expression in the liver tissue of GLP-1 group were significantly higher, while malondialdehyde content was significantly lower than that of model group. GLP-1 receptor agonist reduces insulin resistance and liver oxidative stress injury in diabetic rats with nonalcoholic liver disease.
