1.Experimental study on the glucagon-likepeptide 1 receptor agonist modulation of insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease
Zhigang YI ; Wenan GUO ; Nanjing GUO ; Yufei ZHU ; Bin HUANG
Chinese Journal of Endocrinology and Metabolism 2017;33(3):228-232
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.
2. Effects of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction
Huiyao LU ; Xunfa XU ; Jiayin GUO ; Wenan ZHAO ; Zhimin LIN ; Wenwen LAI
Chinese Journal of Geriatrics 2019;38(9):1048-1052
Objective:
To explore the effect and mechanism of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction.
Methods:
The acute myocardial infarction (AMI) rat model was established by ligating anterior descending branch of coronary artery for one week.A total of 60 adult male rats in SPF grade with AMI were randomized into the Sacubitril/Valsartan group and the model group, who were gavaged with Sacubitril/Valsartan (68 mg/kg, once daily, n=30) versus with normal saline once daily(n=30) for 4 weeks.Twenty-four hours after the last treatment, the left ventricular cardiac function was examined by echocardiography, and pathological changes of the left ventricle were observed under light microscope.The degree of myocardial fibrosis was quantitatively analyzed by picric acid-sirius scarlet staining.Myocardial cells and fibroblasts from rat pups of the same species were prepared in vitro and were divided into the control group, AngⅡ group, LBQ657 group, valsartan group and LCZ696 group.3[H]-leucine incorporation and 3[H]-proline incorporation were used to detect the myocardial hypertrophy and fibrosis.
Results:
There was no significant difference in left ventricular function between the the model group and the Sacubitril/Valsartan group before medication (
3.Correlation between ipsilateral posterior cerebral artery laterality and outcome in patients with acute ischemic stroke in the middle cerebral artery territory
Qian GUO ; Shugang CAO ; Tingting GE ; Jun HE ; Rongfeng WANG ; Mingwu XIA ; Wenan XU
International Journal of Cerebrovascular Diseases 2018;26(6):418-421
Objective To investigate the correlation between ipsilateral posterior cerebral artery laterality (PCAL) and the outcomes in patients with ischemic stroke in the middle cerebral artery (MCA) territory. Methods From June 2015 to December 2016, patients with acute ischemic stroke in the MCA territory admitted to the Second People's Hospital of Hefei were enrolled. Magnetic resonance angiography (MRA) was used to assess PCAL. The outcome was evaluated by the modified Rankin scale at 3 months after onset. 0-2 was defined as good outcome and > 2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results A total of 111 patients with ischemic stroke in MCA territory were enrolled, including 47 (42. 3%) PCAL and 30 (27. 0%) poor outcomes. The baseline NIHSS score in the PCAL group was significantly lower than that in the non-PCAL group (5. 13 ± 3. 29 years vs. 7. 03 ± 5. 676 years, t = 2. 058; P = 0. 042). There were significantly differences in the proportion of diabetes mellitus (29. 6% vs. 10. 0%; χ2 = 4. 583, P = 0. 032), PCAL (51. 9% vs. 16. 7%;χ2 = 11. 101, P = 0. 001) and smoking (25. 9% vs. 13. 3%; χ2 = 4. 943, P = 0. 026), as well as age (63. 9 ± 11. 8 years vs. 71. 0 ± 6. 7 years; t = 2. 688, P = 0. 007), baseline diastolic blood pressure (89 ± 13 mmHg vs. 82 ± 10 mmHg; t = -2. 249, P = 0. 025; 1 mmHg = 0. 133 kPa) and baseline NIHSS score (5. 02 ± 3. 67 vs. 9. 47 ± 6. 20; t = 3. 883, P < 0. 001) between the good outcome group and the poor outcome group. Multivariate logistic regression analysis showed that PCAL was associated independently with good outcome (odds ratio [OR] 0. 272, 95% confidence interval [CI] 0. 083-0. 888; P = 0. 031), while advanced age (OR 1. 088, 95% CI 1. 022-1. 157; P = 0. 008) and high baseline NIHSS score (OR 1. 224, 95% CI 1. 077-1. 391; P = 0. 002) were associated independently with poor outcome. Conclusion PCAL is associated independently with good outcome in patients with ischemic stroke in MCA territory.
4.GLP-1 agonist protects myocardial hypoxia-reoxygenation injury through PI3K/ Akt signaling pathway: an experimental study
Zhigang YI ; Jinhan CHEN ; Jin LI ; Wenan GUO ; Juan WU ; Shangmeng HUANG
Chinese Journal of Endocrinology and Metabolism 2018;34(1):61-66
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.