Effects of genistein on Nrf2/HO-1 pathway in myocardial tissues of diabetic rats / 中南大学学报(医学版)

To investigate the effects of genistein (Gen) on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in myocardial tissues of diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into 4 groups: a normal control (NC) group, a diabetic control (DM) group, a low-dose Gen treatment (L-Gen) group, and a high-dose Gen treatment (H-Gen) group (n=8). Intraperitoneal injection of streptozotocin was utilized to induce diabetic rat model. After the establishment of diabetic model, the rats in L-Gen and H-Gen groups were intragastric administration with 10 and 50 mg/kg Gen solution. Following 8 weeks, the left ventricular hemodynamic parameters and fasting blood glucose (FBG) levels were measured. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in myocardial tissue were determined. The ultrastructure of myocardium was observed under transmission electron microscopy. The expression of HO-1 at mRNA level in myocardial tissue was detected by RT-PCR. The protein levels of Nrf2 and HO-1 in myocardial tissue were detected by Western blotting. 
 Results: Compared with the NC group, left ventricular systolic pressure (LVSP), maximal rise/fall rate of left ventricular pressure (±dp/dtmax), and the levels of GSH-Px, SOD and CAT were decreased (all P<0.01), while the left ventricular end-diastolic pressure (LVEDP), FBG and MDA were increased (all P<0.01) in the DM group. The myocardial ultrastructure was obviously damaged, and the expressions of myocardial Nrf2 and HO-1 were significantly decreased (both P<0.01) in the DM group. Compared with the DM group, there was no difference in FBG in the L-Gen group, while ±dp/dtmax and LVSP were significantly increased (all P<0.05), and LVEDP and MDA were decreased (P<0.05 or P<0.01), and the levels of GSH-Px, SOD and CAT were increased (P<0.05 or P<0.01) in the L-Gen group. The myocardial ultrastructure damage was alleviated and the expressions of Nrf2 and HO-1 were increased (both P<0.01) in the L-Gen group. Compared with L-Gen group, the aforementioned indexes were improved in the H-Gen group (P<0.05 or P<0.01).
 Conclusion: Genistein exerted antioxidant effects on myocardial injury in diabetic rats, and the mechanisms might be related to regulating the Nrf2/HO-1 pathway and enhancing the activities of antioxidant enzymes in myocardial tissues.

Effect of hydrogen sulfide on inducible nitric oxide synthase in kidneys of Type Ⅰ diabetic rats / 中南大学学报(医学版)

Objective:To investigate effects of hydrogen sulfide (H2S) on inducible nitric oxide synthase (iNOS) in kidneys of Type 1 diabetic rats.Methods:Thirty-two male SD rats were randomly divided into four groups:A normal control (NC) group,a diabetes mellitus (DM) group,a NaHS (NaHS+DM) group,and a NaHS control (NaHS) group (n=8 per group).Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg).After successful establishment of models,the rats in NaHS+DM and NaHS groups were injected with NaHS solution (56 μmol/kg) intraperitoneally.Eight weeks later,the activities of total nitric oxide synthase (T-NOS) and iNOS,as well as the level of nitric oxide (NO) were detected in serum and renal tissues,respectively,The activity of glutathione peroxidase (GSH-Px) was determined in renal tissues,The ultrastructures of renal tissues were observed by transmission electron microscope,The protein expression ofiNOS in renal tissues was detected by Western blot.Results:Compared with the NC group,there was no significant difference in the various indexes in the NaHS group (P＞0.05).However,in the DM group,the activities of T-NOS and iNOS,and the level of NO were all increased significantly in serum and renal tissues,while the activity of GSH-Px was decreased in renal tissues.Under the electronic microscope,the thickening of the glomerular capillary basement membrane,the proliferation of mesangial matrix,and the foot fusion were observed.The protein expression ofiNOS was increased obviously in renal tissues in the DM group (P＜0.01).Compared with the DM group,the activities of T-NOS and iNOS and the level of NO were all decreased in serum and renal tissues,while the activity of GSH-Px was increased in renal tissues in the NaHS+DM group (P＜0.01).The renal ultrastructural damages were ameliorated obviously.The protein expression ofiNOS was decreased significantly (P＜0.01).Conclusion:H2S exerts a protective effect on kidney injury in type 1 diabetic rats.The mechanism might be related to inhibition of iNOS activity and protein expression,in turn leading to reduction of NO content in renal tissues.

Effect of hydrogen sulfide on cardiac myosin light chain kinase expression in diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of hydrogen sulfide (H2S) on cardiac myosin light chain kinase (MLCK) expression in diabetic rats.
@*METHODS@#A total of 32 male SD rats were randomly divided into a normal control group (NC group), a diabetic control group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8 in each group). Intraperitoneal injection of streptozotocin was utilized to establish Type 1 diabetic rat model. The diabetic rats in the DM+NaHS and NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. Eight weeks later, the ventricular hemodynamic parameters, the ratio of heart weight/body weight (HW/BW ratio), the levels of lactate dehydrogenase (LDH) and creatine kinase MB isozyme (CK-MB) in serum were determined. The ultrastructures of myocardium were observed under electron microscopy. The expressions of MLCK mRNA and protein level in myocardium were detected by RT-PCR and Western blot, respectively.
@*RESULTS@#Compared with the NC group, there was no significant difference in the various indexes in the NaHS group (all P>0.05). The function of left ventricular contract and relaxation were decreased obviously in diabetic rats, while the HW/BW ratio was increased (all P<0.01). The levels of LDH and CK-MB were increased (both P<0.01) in serum, while the levels of MLCK mRNA and protein were decreased significantly (both P<0.01) in myocardial tissues. Compared with the DM group, the left ventricular hemodynamic parameters and myocardial ultrastructure damage were improved in the DM+NaHS group, while the HW/BW ratio was decreased (all P<0.05). The levels of LDH and CK-MB were decreased (both P<0.01), while the levels of MLCK mRNA and protein were increased significantly (both P<0.01).
@*CONCLUSION@#H2S can protect myocardium in diabetic rats, which may be associated with upregulation of cardiac MLCK.

Effects of hydrogen sulfide on contraction capacity of diaphragm from type 1 diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats.
@*METHODS@#Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. 8 weeks later, the diaphragm contractility was assessed by isolated draphragm strips perfusion. The peak twitch tension (Pt), maximum tetanic tension (Po) and maximal rates of contraction/relaxation (±dT/dtmax) were determined. The alterations in diaphragm ultrastructure were observed under electron microscopy. The diaphragm weight/body weight (DW/BW) was measured. The activities of succinic dehydrogenase (SDH), lactate dehydrogenase (LDH) and sarcoplasmic reticulum Ca2+ ATPase (SERCA) were analyzed by spectrophotometric method. The mRNA levels of SERCA and prospholamban (PLB) in diaphragm were detected by RT-PCR.
@*RESULTS@#Compared with the NC group, there was no significant change in all measured index in the NaHS group (P>0.05), while Pt, Po and ±dT/dtmax were significantly decreased in the DM group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the diaphragm. The DW/BW ratio and the activities of SDH, LDH and SERCA were decreased. The SERCA mRNA was decreased, while PLB mRNA was increased. Compared with the DM group, the diaphragm contractility and ultrastructure damage were improved in the DM+NaHS group. The DW/BW ratio and the activities of SDH, LDH and SERCA were increased. The SERCA mRNA was increased, while PLB mRNA was decreased (all P<0.05).
@*CONCLUSION@#H(2)S can enhance the contraction capacity of diaphragm in type 1 diabetic rats, which is involved in regulating the activities of biological enzymes and the gene expressions of calcium regulatory proteins.

Protective effects of hydrogen sulfide on diaphragmatic muscle of Type 1 diabetic rats and its anti-apoptotic mechanisms / 中南大学学报(医学版)

OBJECTIVE@#To explore the protective effects of hydrogen sulfide (H2S) on diaphragmatic muscle of Type 1 diabetic rats and its anti-apoptotic mechanism.
@*METHODS@#Thirty male Sprague Dawley rats were randomly divided into a control group, a diabetes group and a treatment group (n=10 per group). Streptozotocin (i.p.) was utilized to establish a rat model of Type 1 diabetes mellitus (DM). The DM rats were treated with NaHS solution (i.p.). After 8 weeks, the diaphragmatic muscle contractility was assessed by isolated diaphragmatic strips experiments. The peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT) and maximal rates of contraction/relaxation (±dT/dtmax) were measured. The alterations of diaphragmtic ultrastructure were observed by electron microscopy. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and caspase-3 were analyzed by spectrophotometric method. The expressions levels of Bcl-2 and Bax mRNA in diaphragmatic muscle were detected by RT-PCR.
@*RESULTS@#Compared with the control group, in the diabetic group, the Pt, Po and ±dT/dtmax were significantly reduced (all P<0.01), while CT and 1/2RT were significantly increased (both P<0.01); ultrastructure in the diaphragmatic muscle were obviously changed; the content of MDA and the activity of caspase-3 were increased (both P<0.01), while the activity of SOD was decreased (P<0.01); the ratio of Bcl-2/Bax at mRNA level was decreased (P<0.01). Compared with the diabetes group, in the treatment group, the diaphragm contractility and ultrastructural damage were improved; the content of MDA and the activity of caspase-3 were decreased (P<0.05, P<0.01 respectively), while the activity of SOD was increased (P<0.01), the ratio of Bcl-2/Bax at mRNA level was also increased (P<0.01). 
@*CONCLUSION@#The exogenous H2S can protect diaphragmatic muscle of Type 1 diabetic rats, which is related to reducing oxidative damage and suppressing cell apoptosis.

Effect of soybean isoflavones on heart function of rats with adriamycin-induced heart failure / 中西医结合学报

OBJECTIVE: To observe the protective effect of soybean isoflavones (SI) on the heart function of the rats with adriamycin induced heart failure. METHODS: Thirty adult male SD rats were divided into 5 groups:normal control (NC) group, adriamycin (ADR) group, L-SI group, M-SI group and H-SI group. SI of 30, 60, 120 mg.kg(-1).d(-1) was orally administered through a stomach tube once a day for 6 days in L-SI group, M-SI group and H-SI group, respectively. The other two groups were given the same amount of normal saline the same way. Then ADR of 10 mg/kg was given intraperitoneally once to copy the model of heart-failure. The MedLab-U/4c biological signal collecting system was used to record and analyze the LVSP of the rats. The pathological changes of the cardiomyocytes were observed. RESULTS: As compared with NC group, the LVSP,+/-dp/dt max, Vpm of the ADR group were significantly lower (P<0.05 or P<0.01), but those of the H-SI group were markedly higher than those of the ADR group (P<0.01). Electron microscopic morphometry of the heart samples of the rats in ADR group revealed typical alterations, consisting an increase of collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration of myofilaments and Z-lines of myofibers, and myofibrillar degeneration. SI of 120 mg.kg(-1).d(-1) treatment could prevent the loss of myofibrillae and the reduction of myocyte diameter, and the degeneration of myofilaments and Z-lines were reversed by SI. CONCLUSION: SI of 120 mg.kg(-1).d(-1) treatment can relieve the toxic effect of ADR on myocardium, and also obviously improve the cardiac contractility of heart-failure rats.

An Experimental Study on PBL Combined LBL Applied to Physiology Teaching / 中华医学教育探索杂志

An experimental study of two approaches of teaching——problem-based learning(PBL) combined with lecture-based learning(LBL) and LBL only——was conducted respectively in two classes of 2003 college students.It was proved that PBL combined with LBL has an obvious advantage over LBL only(P

Effects of Soy Isoflavones on NO Content and NOS Activity in Myocardial Tissues of Diabetic Rats / 中药新药与临床药理

Objective To observe the effects of soy isoflavones (SI) on NO content and NOS activity in myocardial tissues of diabetic rats. Methods Forty-eight SD rats were randomly divided into six groups: normal control group (NC), diabetic control group (DC), SI groups in low, moderate and high doses respectively (L-SI, M-SI, H-SI) and nilestriol group (NI). Except the NC group, the rats were given streptozotocin (STZ) 55mg?kg-1 intraperitneally (ip). From the 7th week, SI in the dosage of 30, 60, 120 mg?kg-1?d-1 was respectively given to L-SI, M-SI, H-SI groups by gastric gavage, nilestriol 0.2 mg?kg-1?per week was given to NI group,and 0.5%CMC-Na10 ml?kg-1?d-1 was given to NC and DC groups. After treatment, fasting blood sugar level, body weight, serum lactate dehydrogenase (LDH)and creatine kinase (CK) contents, and NOS activities and NO content in myocardial homogenate were measured. Results 1) LDH and CK contents in serum were significantly higher in DC group than those in NC group. Compared with DC group, LDH and CK were significantly decreased in M-SI and H-SI groups (P