RESUMO
OBJECTIVE：To observe the safety and other related indexes of canagliflozin in the treatment of type 2 diabetes complicated with high risk of cardiovascular disease. METHODS ：Totally 306 patients，admitted to Hainan Provincial People ’s Hospital and Haikou People ’s Hospital ，with type 2 diabetes complicated with high risk of cardiovascular disease were selected from Dec. 2018 to Apr. 2019. They were divided into observation group （153 cases）and control group （153 cases）according to random number table . The control group was treated with in sulin，metformin or sulfonylureas conventional hypoglycemic therapy ， and the observation group was treated with Canagliflozin tablets 100 mg，once a day ，po，on the basis of control group. The course of treatment was 1 year in both groups. The levels of HbA 1c，BMI，SBP，DBP and eGFR before and after treatment were observed in 2 groups，and the incidence of safety （including death from cardiovascular causes ，myocardial infarction ，ischemic stroke ， hospitalization for heart failure and death from any cause etc. ） after treatment and serious ADR/ADE （including hypogly- cemia，diabetic ketoacidosis ，fracture，acute kidney injury 68622942。E-mail：zhaixin0123@126.com etc.）during the treatment were recorded. RESULTS ：A total of 5 patients in the control group were not followed up ， in which 3 quited and 2 were lost ；and 4 patients in the observation group were not followed up ，in which 1 quited and 3 were lost . Before treatment ，there were no statistical significance in the levels of HbA 1c，BMI，SBP，DBP and eGFR between 2 groups（P＞0.05）. After treatment ，HbA1c levels of 2 groups，BMI and SBP of observation group were all significantly lower than those before treatment with the same group ；HbA1c level and SBP of observation group were significantly lower than those of control group （P＜0.05）. eGFR levels of 2 groups after treatment were significantly higher than before treatment with the same group ，while the observation group was significantly higher than that of contrl group. The incidence of death from cardiovascular causes and death from any cause in observation group were significantly lower than control group （P＜0.05）. There were no statistically significant differences in other safety indexes and the incidence of serious ADR/ADE between 2 groups（P＞0.05）. CONCLUSIONS ：Canagliflozin can significantly reduce the incidence of death from cardiovascular causes and death from any cause in type 2 diabetes patients complicated with high risk of cardiovascular disease，ameliorate blood glucose and blood pressure ，and do not increase the occurrence of serious ADR/ADE.
RESUMO
OBJECTIVE： To investigate the protective effect and potential mechanism of epigallocatechin gallate （EGCG） on myocardial ischemia-reperfusion injury. METHODS： H9C2 cardiomyocytes were treated with tert-butyl hydroperoxide （TBHP） to establish ischemia-reperfusion cell model. The cell viability was measured by MTS after pretreated with different doses of EGCG （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol/L）， and the survival rate was calculated. The expression of apoptotic proteins （Bcl-2， Bax） in cardiomyocytes pretreated with different doses of EGCG （100， 200 μmol/L） were detected by Western blotting. Male C57BL/6 mice were randomly divided into sham operation group， model group and EGCG group （5 mg/g）， with 15 mice in each group. Sham operation group and model group were given constant volume of normal saline intragastrically， while EGCG group was given relevant medicine intragastrically， once a day， for consecutive 7 d. Twelve hours after last medication， myocardial ischemia-reperfusion injury model was established by anterior descending coronary artery ligation. The area of myocardial infarction was observed by double staining of Evan’s blue and TTC； the percentage of infarction area to cross-sectional area was calculated；SOD activity and MDA content in serum were determined by WST-1 assay； the expression of apoptotic proteins （Bcl-2， Bax） in myocardial tissue were detected by Western blotting， while the phosphorylation levels of signaling pathway related proteins （PI3K， p-PI3K， Akt， p-Akt） were also detected. RESULTS： Cell test results showed that， compared with control group， survival rate and relative expression of Bcl-2 were decreased significantly in model group， while relative expression of Bax was increased significantly （P＜0.05）. Compared with model group， survival rate of cardiomyocyte in 25， 50， 100， 200 μmol/L EGCG groups as well as relative expression of Bcl-2 in 100， 200 μmol/L EGCG groups were increased significantly， while relative expression of Bax in 100， 200 μmol/L EGCG groups were decreased significantly （P＜0.05）. Animal experiments showed that no ischemia of myocardial tissue and enlargement of cardiac cavity were observed in sham operation group. Myocardial infarction was observed in model group. Compared with sham operation group， percentage of infarction area to cross-sectional area， the serum content of MDA， the relative expression of Bax in myocardial tissue and p-PI3K/PI3K， p-Akt/Akt were increased significantly in model group， while SOD activity and relative expression of Bcl-2 were decreased significantly （P＜0.05）. Compared with model group， myocardial infarction area of mice in EGCG group was reduced， the percentage of infarction area to cross-sectional area， the serum content of MDA， the relative expression of Bax in myocardial tissue and p-PI3K/PI3K， p-Akt/Akt were significantly decreased， the activity of SOD activity and the relative expression of Bcl-2 were increased significantly （P＜0.05）. CONCLUSIONS： EGCG can protect against myocardial ischemia-reperfusion injury， the mechanism of which may be associated with inhibiting the apoptosis of myocardial cells， improving oxidation stress， regulating the expression of apoptotic protein， reducing the phosphorylation level of PI3K/Akt signaling pathway-related proteins.