| Objective Type 2 diabetes mellitus(T2DM) is a kind of systemic metabolic diease characterized by insulin resistance and body’s inadequate production of insulin, increased the risk of cardiovascular disease in patients with diabetes, more than 60% of diabetes mellitus(DM) patients suffer and may eventually die from complications of cardiovascular disease. The risk of death from cardiovascular diseases in DM patients is two times that of the normal blood glucose. Myocardial ischemia / reperfusion(reperfusion I/R, ischemid) injury is the damage of myocardial tissue induced by ischemia and hypoxia on the basis of myocardial ischemia and hypoxia, and finally induces apoptosis and necrosis of cardiomyocytes. Sufentanil is commonly used opioids that has clinically strong analgesic effect, a slight effect on the hemodynamics, widely used in clinical cardiovascular anesthesia. Animal studies demonstrated that opioid sufentanil after treatment dose-dependently reduces myocardial ischemia-reperfusion injury, and diabetes factors was able to cancel the protection, study showed that the factors may lead to diabetes endoplasmic reticulum stress( ERS) enhanced protection related to the role, ERS-induced apoptosis pathway activation, the impact of opioids. Ursodeoxycholic acid(UDCA) is currently studied endoplasmic reticulum stress inhibitor, can reduce the extent of the reaction of endoplasmic reticulum stress. This study was designed to investigate the ERS inhibitors ursodeoxycholic acid treatment after recovery sufentanil reduce the role of type 2 diabetic rats with myocardial ischemia and reperfusion injury.Methods Male SPF SD rats with original weight ranged from 250 to 300 gram, were randomly divide into 3 group(n=10):sham group(NDM-S group), ischemia-reperfusion group(NDM-I/R group), sufentanil treated group(NDM-SP group). Another type 2 diabetes model 60 male SD rats, the same rats were divided into six groups(n = 10): sham group(DM-S group), ischemia-reperfusion group(DM-I/R group), sufentanil treated group(DM-SP group), ursodeoxycholic acid pretreatment sham group(DM-US group), ursodeoxycholic acid pretreatment group(DM-UP group) and bear deoxycholate acid pretreatment and post-treatment sufentanil group(DM-USP group). The groups of DM received highi-fat diet for 4weeks, then renceived 35mg/kg STZ intraperitoneal injection, then received another 4 weeks for high-fat diet. By ligating the left anterior descending artery 30 min, 120 min reperfusion way to create a model of myocardial ischemia and reperfusion. DM-S group,NDM-S group and DM-US group in the left anterior descending artery threading, without ligation; NDM-SP group, DM-SP group and DM-USP group at 5 min before reperfusion were injected through the femoral vein sufentanil 1μg/kg; the rest groups were treated with saline for Comparison. DM-US group, DM-UP group, DM-USP group, preoperative administration of ursodeoxycholic acid 100 mg/kg orally for one week. Myocardial ischemia before(T0), ischemia 30 min(T1), reperfusion recording HR and MAP 120 min(T2) time. Now when sacrificed 120 min reperfusion in rats, measured myocardial infarct volume; apical tissue, Western blot assay endoplasmic reticulum stress-related molecules of glucose regulated protein GRP78/Bip expression levels.Results HR rats at each time point difference was not statistically significant(P > 0.05); compared with NDM-S group, NDM-I/R group MAP decrease(P < 0.05); compared with NDM-I / R group, NDM-SP MAP group increased(P < 0.05). Compared with the NDM-S group, NDM-I / R group, myocardial infarct size increased(P < 0.05); Compared with I / R group, NDM-SP reduced myocardial infarct size(P < 0.05); and NDM-S group, NDM-I / R group, myocardial GRP78 expression increased(P < 0.05), compared with NDM-IR group, NDM-SP myocardial tissue GRP78 downregulated(P < 0.05). Compared with the DM-S group, DM-IR, DM-SP, DM-UP group MAP decrease(P < 0.05), and upregulation of GRP78 myocardial tissue(P < 0.05), DM-USP group no significant difference(P > 0.05); and DM-SP group, DM-UP group, DM-USP MAP group were elevated myocardial tissue GRP78 downregulated(P < 0.05).Conclusion The study found that endoplasmic reticulum stress inhibitor of ursodeoxycholic acid can attenuate myocardial ischemia-reperfusion injury by sufentanil postconditioning in rats of type 2 diabetes mellitus. |
PDF Full Text Request