[Objective] To study the pharrnacodynamic effect of Bao Xin Kang on animal models with cardiac insufficiency (CI) . [Methods] CI animal models were established by constricting the abdominal aortae in rabbits. The pathological results in different groups were compared. The hemodynamics indices such as LVEDP and?dp/dtmax and NO level were measured. [Results] Compared with the model group, the high dose of Bao Xin Kang can lessen the hyperplasia and hypertrophy of the myocardium and relieve the pulmonary edema in animals and improve the hemodynamics indices. LVEDP was decreased ( P

BACKGROUND: 5-azacytidine (5-Aza) has been frequently used to induce bone marrow mesenchymal stem cells (BMSCs)differentiation into cardiomyocyte.OBJECTIVE: To observe expression of cardiomyocyte-related receptors in cardiomyogenic differentiation of rat BMSCs.METHODS: BMSCs of passage three were assigned to four groups: group Ⅰ: L-DMEM solution alone was replaced; Ⅱ:L-DMEM solution was replaced after induction of 100 mg/L AST+5 μmol/L 5-Aza for 24 hours; group Ⅲ: L-DMEM solution wasreplaced after induction of 10 μmol/L 5-Aza for 24 hours; and group Ⅳ: L-DMEM solution was replaced after induction of 5 μmol/L5-Aza for 24 hours. Culture medium was replaced every 3 days in each group. Differentiated cells were identified after 30 days ofinduction.RESULTS AND CONCLUSION: Expression of cardiomyocyte specific proteins Nkx2.5, cTnT and Desmin was detected in groupsⅢ, Ⅳ and Ⅱ after induction compared with group Ⅰ , with significant differences (P < 0.01). The amount of cTnT and Desminexpression expression was significantly higher in groups Ⅱ and Ⅲ compared with group Ⅳ (P < 0.01). The level of Nkx2.5expression was significantly higher in groups Ⅱ (P < 0.01) and Ⅲ (P < 0.05) compared with group Ⅳ. No Nkx2.5, cTnT andDesmin espression was detected in group Ⅰ. After induction for 2 weeks, cells with spontaneous contractility were observed ingroups Ⅱ and Ⅲ, indicating differentiation towards cardiomyocyte after induction. Results demonstrated that induction effectswere similar between 100 mg/L AST+5 μmol/L 5-Aza and 10 μmol/L 5-Aza. This may contribute to cytoprotective effects of AST,which can promote vascular endothelial cell proliferation, enhance celss tolerance to 5-Aza-induced cytotoxicity and upregulatecardiac-specific protein expression.

Objective To investigate the effect of allogeneic bone marrow mesenchymal stem cell transplantation on the cardiac structure and function in rats with acute myocardial infarction. Methods Thirty SD rats were randomly divided into blank group, model group, and stem cells group, 10 rats in each group. The model group received left coronary artery ligation to induce acute myocardial infarction, and the stem cells group received myocardial injection of stem cells after coronary artery ligation. After four weeks, cardiac function and heart tissue pathological changes were observed. Results In the model group, left ventricular end-diastolic volume, left ventricular end-systolic volume and end dias-tolic volume were increased, and left ventricular ejection fraction, left ventricular fractional shortening rate and cardiac output were decreased as compared with the normal group and the stem cells group (P < 0. 05). The results of pathologi-cal examination showed that myocardiac fibers dissolved or even disappeared, and fibric proliferation and sear occurred in the model group; in the stem cells group, the arrangement of myocardiae fibers was in disorder and there were a few pro-liferated fibers and scar compared with the normal group. Conclusion Allogeneic bone marrow mesenchymal stem cell transplantation can improve the cardiac structure and function in rat model of acute myocardial infarction.

AIM:To investigate the effects of Xinkang recipe on myocardial miR-25-3p expression and sarco-plasmic reticulum calcium ATPase 2a ( SERCA2a) activity in heart failure rats .METHODS:Male SD rats were randomly divided into normal group , sham group , model group , Xinkang recipe group ( Xinkang group ) , and captopril group .The heart failure rat model was induced by intraperitoneal injection of doxorubicin .Distilled water , Xinkang recipe and capto-pril were administrated by gastric gavage for 35 d, respectively .The indexes of cardiac function and plasma level of brain natriuretic peptide (BNP) were measured.The SERCA2a activity was determined by the inorganic phosphorus method . The myocardial protein expression of SERCA 2a and phospholamban ( PLB) was detected by Western blot .The myocardial expression of miR-25-3p was detected by stem-loop RT-qPCR.RESULTS:Cardiac output (CO), left ventricular fraction-al shortening ( LVFS) and left ventricular ejection fraction ( LVEF) in Xinkang group and captopril group were significantly higher while the plasma levels of BNP were significantly lower than those in model group (P<0.01).The myocardial ex-pression levels of miR-25-3p in Xinkang group and captopril group were significantly lower while the myocardial protein le -vels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Xinkang group were significantly higher than those in model group (P<0.05), and no significant change was observed between captopril group and model group .CONCLUSION:Xinkang recipe therapy may improve car-diac function in heart failure rats , which may be related to inhibiting the expression of miR-25-3p, increasing the SER-CA2a/PLB ratio and enhancing SERCA 2a activity in the myocardium .

In order to protect the trial subjects' rights and benefits in drug clinical trials,we must pay special attention to the risk and benefit of the trial subjects(striving to minimize the risk and maximize the benefit),ensure the trial subjects' complete realization of the clinical trials and the successive informed consent,pay special attention to the protection of the specific trial subjects,and avoid the conflict of interests.

Objective: To observe the effect of bisoprolol on cardiac function in heart failure (HF) rats and to explore the mechanism. Methods: The experimental rats were divided into 6 groups: Control group, with normal healthy rats, Sham group, the rats received intraperitoneal injection of normal saline; chronic heart failure (CHF) model was successfully established in 40 rats and divided into 4 groups: CHF group, CHF+bisoprolol (Bis) group, CHF+captopril (Cap) group and CHF+Bis and Cap group.n=10 in each group. The cardiac function was observed among different groups; plasma BNP level was measured by ELISA, myocardial miR-25-3p expression was examined by RT-PCR, protein expressions of SERCA2a and phospholamban (PLB) were detected by Western blot analysis and SERCA2a activity was determined by inorganic phosphorus method. Results: Compared with Control group, CHF group showed decreased cardiac output (CO), left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), reduced expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while increased plasma BNP and miR-25-3p expression, allP<0.01. Compared with CHF group, CHF+Bis, CHF+Cap and CHF+Bis and Cap groups had increased CO, LVFS, LVEF, elevated expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while decreased plasma BNP and miR-25-3p expression, allP<0.05.Conclusion: Bisoprolol could improve cardiac function in HF rats, which might be related to down regulating myocardial miR-25-3p expression, up regulating myocardial protein expressions of SERCA2a, PLB and enhancing SERCA2a activity.

Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart fail-ure.Methods Male SD rats were randomly divided into normal control group (control group), sham operation group ( sham group ) , model group , bisoprolol group ( Bis group ) , captopril group ( Cap group ) and bisoprolol plus captopril group[(Bis+Cap)group], heart failure rat model was induced by intraperitoneal injections of doxorubicin .Distilled water, bisoprolol, captopril or bisoprolol plus captopril were administrated by gastrogavage for 35 days, respectively. Indices of cardiac function and plasma levels of B-type natriuretic peptide ( BNP) were measured , myocardial expres-sion of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban (PLB) were detected by Western blot , myocardial SERCA2a activity was determined by the inorganic phosphorus method . Results Cardiac function in model group decreased significantly while plasma levels of BNP were significantly higher than those of control group ( P<0.01 ) .Myocardial expression of miR-25-3p in model group was significantly higher while myocardial levels of SERCA 2a and PLB,SERCA2a activity were significantly lower than those of con-trol group(P<0.01).Cardiac function in Bis group , Cap group and Bis +Cap group improved significantly while plasma levels of BNP were significantly lower than those of model group ( P<0.01 ) .Myocardial expression of miR-25-3p in Bis group, Cap group and Bis +Cap group were significantly lower while myocardial levels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Bis group and Bis +Cap group were significantly higher than those of model group ( P<0.05 ) .Conclu-sions Bisoprolol therapy improves cardiac function in rats with heart failure , which may be related to inhibition of myocardial miR-25-3p, increasing myocardial SERCA2a and PLB levels, enhancing SERCA2a activity.

【Objective】To observe the in-vitro effect of panax notoginseng saponins(PNS) on bone marrow mesenchymal stem cells(MSCs) proliferation and on inducing MSCs to differentiate into cardiomyogenic cells.【Methods】MSCs were isolated from adult SD rats,and then were cultured and cloned by density gradient method and adhesive cultivation.The cell surface markers of MSCs were detected with flow cytometer.The effect of PNS on MSCs proliferation was observed with methyl thiazolyl tetrazolium(MTT) assay.The 8th generation of continuous cultured MSCs was used to observe the in-vitro differentiation of cardiomyogenic cells.The cardiomyogenic cells were identified under phase contrast microscope by immunohistochemical method and reverse transcription-polymerase chain reaction(RT-PCR) analysis.【Results】CD44 expression of MSCs was positive while that of CD34 expression of bone marrow hematopoietic stem cells was negative,indicating the success of the MSCs culture.After induction with PNS,the increase of MSCs was obvious as compared with the blank control group,and there existed histological changes of MSCs after in-vitro induction.The expression of specific proteins of Desmin and cardiac troponin I(cTnI) in MSCs was positive,and the results of RT-PCR analysis showed that the expression of myosin heavy chain(MHC) was increased.【Conclusion】PNS can increase the in-vitro proliferation of MSCs and induce MSCs to differentiate into cardiomyogenic cells in vitro,and this will supply experimental evidence of cell transplantation for the treatment of myocardial infarction.

Objective To observe the effects of Tianma Gouteng Yin (TGY) on the proliferation of myocardial fibroblasts of spontaneous hypertensive rat(SHR) stimulated by insulin. Methods The cardiac fibroblasts from one-day-old spontaneously hypertensive rat were primarily cultured and then sub-cultured to 3rd-6th generation,and were identified with light microscopy and immunohistochemical technique. The effect of serum containing TGY on the proliferation of cardiac fibroblasts of SHR treated with insulin was determined by MTT colorimetric assay and 3-H-TdR incorporation,and the cell cycle was analysised with flow cytometer. Results TGY inhibited the proliferation of cardiac fibroblasts induced by insulin. Insulin can stimulate the proliferation of fibroblasts by promoting the cell cycle transfer from G0/G1 period to S period and increasing the synthesis of cell DNA. Compared with the model group,the percentage of the cells at G0/G1 period was much higher,while the percentage of the cells at S period was much lower in TGY group. Conclusion TGY has the effect on inhibiting the proliferation of cardiac fibroblasts and inhibiting the cell cycle transfer from G0/G1 period to S period,which may be one of its therapeutic and protective mechanisms for hypertension and myocardial fibrosis in clinic.

Objective To observe the effect of Xuefu Zhuyu Decoction(XZD) for the intervention of myocardial fibrosis of coronary heart disease(CHD) patients with blood stasis syndrome,and to explore its mechanism.Methods Sixty CHD patients with blood stasis syndrome were equally randomized into XZD group and placebo group.Both of the two groups were given western basic medicine.Meanwhile,XZD group received oral use of XZD and the placebo group received oral use of decoction of Fructus Hordei Germinatus,Fructus Setariae Germinatus and Radix Glycyrrhizae additionally.Changes of serum precollagen Ⅲ(PCⅢ),laminin(LN),hyaluronic acid(HA),endothelin(ET) and nitric oxide(NO) were observed before and after treatment.Results Serum levels of PCⅢ,LN,HA and ET were decreased,and NO was increased in the two groups after treatment(P