| Objectives Effect and mechanism of paeoniflorin on myocardial injury in type 2 diabetes mellitus（T2DM）rats.Methods In this study,the SD rats were divided into normal group,model group,metformin group(90 mg·kg-1)and peonidin high,medium and low dose groups(90,60and 30 mg·kg-1)randomly.The diabetic rat model was established by feeding the rats with high-fat diet and intraperitoneal injection of streptozotocin(30 mg·kg-1)in all groups except for the normal group.When the fasting blood glucose value is greater than or equal to 11.1 mmol·L-1,the modeling is successful.After successful modeling,rats in each administration group were given different volumes of drugs.Rats in the normal group and model group were given the same volume of normal saline.Rats in each group were gavaged once a day for 4 weeks.After the administration,the rats’body weight and fasting blood glucose（FBG）were measured and oral glucose tolerance test was performed;the rats’serum glycated serum protein（GSP）,total cholesterol（T-CHO）,triglyceride（TG）,glutathione peroxidase（GSH-Px）,superoxide dismutase（SOD）,malondialdehyde（MDA）,creatine kinase isoenzyme-MB（CK-MB）,and cardiac troponin I（c Tn-I）were measured.The levels of Bcl-2,Bcl-2-associated X protein（Bax）and caspase-3 protein expression in rat myocardial tissues were measured by immunohistochemistry and Western blot,respectively caspase-3 protein expression levels in rat myocardial tissue.Results 1 The rats in the control group gained weight,and were observed with smooth body hair and were active.In contrast,the rats in the model group lost weight and had disheveled and withered hair,were less active and less active.Compared with the rats of model group,the rats in the metformin group and all doses of paeoniflorin showed improvement.2 Compared with the rats of control group,fasting blood glucose(25.41±2.14 mmol·L-1)and oral glucose tolerance（50.38±1.64）were increased in the model group（P<0.01）;compared with the model group,fasting blood glucose was observed with a reduction in the metformin group and the high and low dose groups of peonidin(16.50±1.52 mmol·L-1,21.70±1.95 mmol·L-1,22.30±1.93 mmol·L-1,24.55±2.22mmol·L-1,P<0.05 or P<0.01),and oral glucose tolerance decreased in the metformin and peonidin high and low dose groups（47.17±3.48,41.29±1.60,45.80±2.90,46.04±3.45,P<0.05 or P<0.01）3 Compared with the rats in control group,the serum levels of GSP(1.55±0.07 mmol·L-1),T-CHO(2.42±0.22 mmol·L-1),TG(2.73±0.14 mmol·L-1)and MDA(12.09±1.01 mmol·m L-1)were increased in the model group（P<0.01）,and GSH-Px(664.60±27.92 U·m L-1)and SOD(51.02±4.63 U·m L-1)levels were decreased（P<0.01）;compared with the model group,the serum levels of GSP(0.74±0.07 mmol·L-1,0.47±0.04mmol·L-1,0.41±0.04 mmol·L-1,0.57±0.05 mmol·L-1),T-CHO(1.38±0.12 mmol·L-1,1.27±0.11 mmol·L-1,1.55±0.16 mmol·L-1,1.86±0.15 mmol·L-1),TG(1.49±0.15 mmol·L-1,1.49±0.15 mmol·L-1),and TG(1.49±0.15 mmol·L-1,1.55±0.16 mmol·L-1,1.25±0.04mmol·L-1,1.45±0.14 mmol·L-1,1.75±0.33 mmol·L-1),MDA(7.36±2.09 mmol·L-1,6.89±0.89 mmol·L-1,8.92±0.69 mmol·L-1,12.03±0.68 mmol·L-1)levels were reduced（P<0.01）,GSH-Px(852.74±38.83 U·m L-1,843.84±57.95 U·m L-1,789.56±32.69 U·m L-1,762.68±69.21 U·m L-1),SOD(85.29±2.46 U·m L-1,67.99±2.70 U·m L-1,61.24±3.81 U·m L-1,57.51±5.61 U·m L-1)levels were increased（P<0.05 or P<0.01）.4 Compared with the control group,the serum levels of CK-MB(5.64±0.66 ng·m L-1)and c Tn-I(1.66±0.12ng·m L-1)increased in the model group（P<0.05 or P<0.01）;compared with the model group,the serum levels of CK-MB(4.75±0.18 ng·m L-1,4.85±0.37 ng·m L-1,4.94±0.31ng·m L-1,4.94±0.31 ng·m L-1),and c Tn-I(1.28±0.20 ng·m L-1,1.38±0.15 ng·m L-1,1.36±0.12 ng·m L-1)levels were reduced in the serum of rats in the high and low dose groups of paeoniflorin（P<0.05 or P<0.01）.5 The results of HE staining of the heart showed that the myocardial tissue of the model group was relatively irregular,the muscle bundle spacing was widened,and some muscle fibers were broken;Compared with the model group,the pathological morphology of metformin group and paeoniflorin groups was improved.6 Tunel staining showed that compared with the normal group,the apoptosis index of cardiomyocytes in the model group increased（19.12±2.29%,P<0.01）;Compared with the model group,the cardiomyocyte apoptosis index of high,medium and low dose paeoniflorin group decreased(5.98±0.45%,13.40±0.90%,14.19±0.85%,##P<0.01).7 The results of immunohistochemical assay showed that,compared with the normal group,the mean optical density values of Bax（0.1195±0.0112）and caspase-3（0.0476±0.0060）proteins increased（P<0.01）and Bcl-2（0.0147±0.0055）proteins decreased in the myocardial tissue of rats in the model group（P<0.01）;Compared to the model group,the mean optical density of Bax（0.0308±0.0056,0.0380±0.0216,0.0587±0.0218）and caspase-3（0.0380±0.0093,0.0462±0.0161,0.0433±0.0085）proteins in myocardial tissue of rats in the high and low dose groups of paeoniflorin values decreased（P<0.05 or P<0.01）and the mean optical density values increased（P<0.05 or P<0.01）for Bcl-2（0.0354±0.0073,0.0345±0.0133,0.0342±0.0101）proteins.The results of Western blot assay illustrated that the expression levels of Bax（5.22±0.09）and caspase-3（6.68±1.16）were increased（P<0.01）and Bcl-2（2.98±0.16）were decreased（P<0.01）in myocardial tissues of rats in the model group;compared with the model group,paeoniflorin decreased the expression levels of Bax（3.23±0.09）and caspase-3（6.68±1.16）in myocardial tissues of rats.Bax（3.23±0.74,3.42±1.03,5.14±0.56）and caspase-3（4.30±1.18,4.51±1.09,4.68±0.19）protein expression levels（P<0.05 or P<0.01）,and increased Bcl-2（4.48±0.66,4.34±0.60,4.00±0.52）protein expression levels in rat myocardial tissue compared with the model group protein expression levels（P<0.05 or P<0.01）.Conclusions 1 Paeoniflorin can improve the abnormal glucose and lipid metabolism and the ability of anti oxidative stress in T2DM rats.2 Paeoniflorin could reduce the levels of CK-MB and c Tn-I in T2DM rats,so as to improve the morphological structure of myocardium and the damage of myocardial tissue cells in T2DM rats.3 paeoniflorin can inhibit cardiomyocyte apoptosis and regulate Bcl-2/Bax/caspase-3signaling pathway to improve myocardial injury in T2DM.Figure 14;Table 3;Reference 162... |
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