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 explore the effect of Xinkang Tablets on myocardial apoptosis index,collagen volume fraction and sarcoplasmic reticulum Ca2+-ATPase activity of rats with adriamycin-induced heart failure.Methods The chronic heart failure (CHF) SD rat model was established by intraperitoneal injection of doxorubicin.After successful modeling,the rats with CHF were randomly divided into 5 groups,namely model group,western medicine group,and low-,middle-and high-dose of Chinese medicine groups,10 rats in each group.The rats in the above groups were given intragastric administration of distilled water,22.5 μg/kg of Digoxin mixed suspension,9,18,36 g/kg of XinkangTablets,respectively,in the volume of 10 mL/kg of distilled water dilution,once a day,for 5 continuous weeks.Another the same batch of 10 SD rats were randomly allocated to the sham operation group,and were treated with intragastric administration of the same volume of distilled water.And then the apoptotic rate of myocardial cells was measured by TUNEL method,the collagen volume fraction (CVF) was measured after Masson staining,and the sarcoplasmic reticulum Ca2+-ATPase activity was determined by inorganic phosphate assay.Results Compared with the sham operation group,the apoptotic rate of myocardial cells and CVF in the model group were increased(P ＜ 0.01),indicating that the myocardial remodeling occurred in rats with CHF.Compared with the model Group,the apoptotic rate of western medicine group and three Chinese medicine groups was significantly decreased(P ＜ 0.01),suggesting that Digoxin and Xinkang Tablets can relieve apoptosis to certain extent.The CVF in Digoxin group and middle-and high-dose of Chinese medicine groups were lower than those in the model Group (P＜ 0.05 or P＜ 0.01),indicating that Digoxin and Xinkang Tablets can delay the myocardial fibrosis.Last but not least,the SERCA2a activities in the middle-and high-dose of Chinese medicine groups were higher than those in the model group (P ＜ 0.05 or P ＜ 0.01),suggesting that Xinkang Tablets may relieve myocardial remodeling and improve cardiac function through the regulation of SERCA2a activity.Conclusion Xinkang Tablets decrease the apoptotic rate and myocardial cell volume fraction probably through the regulation of SERCA2a activity,which may play a role in counteracting apoptosis and myocardial fibrosis,and ultimately delay the remodeling of the myocardium.

ABSTRACT:Objective To investigate the effects of Xiefei Lishui recipe on left ventricle remodeling in rats with heart failure.Methods Heart failure rat model was induced by intraperitoneal injections of doxorubicin. Rats were randomly divided into sham operation group (sham group),model group,traditional Chinese medicine group (TCM group),captopril group,and digoxin group.Distilled water,TCM [22 g/(kg · d)],captopril [19 mg/(kg·d)],and digoxin [32μg/(kg·d)]were administered by gastrogavage in rats in different groups for 35 days,respectively.Indices of ventricle remodeling and cardiac function,plasma levels of B-type natriuretic peptide (BNP),rennin (REN),angiotensin Ⅱ(AngⅡ)and aldosterone (ALD)were measured.Cardiomyocyte apoptosis index and collagen volume fraction (CVF)were analyzed.We also assayed myocardial mRNA expressions of MMP-2/9 and TIMP-1/2,and their tissue inhibiting factors TIMP-1 and TIMP-2.Results Compared with those in sham group,in model group cardiac function was significantly decreased,which could be significantly increased by TCM or captopril or digoxin,indices of cardiac remodeling were significantly increased,which could be significantly decreased by TCM or captopril (P<0.01 or P<0.05).Plasma levels of BNP,REN,AngⅡ and ALD,cardiomyocyte apoptosis index and CVF in model group were significantly increased,could be significantly decreased by TCM or captopril (P<0.01 or P<0.05).Myocardial mRNA expressions of MMP-2,MMP-9,TIMP-1 and TIMP-2 in model group were significantly upregulated compared with those in sham group, which could be significantly downregulated by TCM (P<0.01 or P<0.05).Conclusion Xiefei Lishui recipe can attenuate left ventricle remodeling and improve cardiac function in rats with heart failure, which may be related to downregulating myocardial mRNA expressions of MMP-2 ,MMP-9 ,TIMP-1 and TIMP-2 in the left ventricle as well as inhibiting cardiomyocyte apoptosis and myocardial fibrosis.

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 .

Objective To evaluate the therapeutic effect of modifiedHuanglian-Jiedudecoction for resistant hypertension and explore its possible mechanism.Methods A total of 90 patients with resistant hypertension were recruited and randomly divided into a treatment group and a control group, 45 patients in each group. The control group was treated with oral administration of irbesartan and hydrochlorothiazide tablets and controlled-release nifedipine tablets, while the treatment group was further added modifiedHuanglian-Jiedu decoction for 4 weeks. Plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) were measured by radioimmunoassay.Rusults The total efficiency according to the TCM syndrome in the treatment group was 86.7%(39/45) which was higher than 64.4%(29/45) in the control group(χ2=4.873,P=0.027). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased after the treatment in both groups ( SBP in the treatment group: 119.26 ± 9.34 mmHgvs.172.11 ± 10.52 mmHg,t=25.201,P<0.01; DBP in the treatment group: 78.18 ± 7.21 mmHgvs.111.12 ± 11.16 mmHg,t=16.631, P<0.01; SBP in the control group: 145.21 ± 7.56 mmHgvs.171.32 ± 11.15 mmHg,t=13.002,P<0.01; DBP in the control group: 93.57±8.13 mmHgvs. 109.89 ± 12.21 mmHg,t=7.463,P<0.01), while the decrease of SBP (t=14.487,P<0.01) and DBP (t=9.501, P<0.01) in the treatment group was more greater than those in the control group. The control rate of blood pressure in the treatment and control groups were 73.3% (33/45) and 55.6% (25/45), respectively, there had no significant difference (χ2=2.376,P=0.123). The plasma ET in the treatment group was significantly decreased than that in the control group (75.68 ± 10.67 ng/Lvs.112.79 ± 12.26ng/L;t=15.317,P<0.05), and CGRP significantly increased (49.87 ± 4.75 ng/Lvs.33.87 ± 7.89 ng/L;t=11.654,P<0.05).Conclusion Modified Huanglian-Jiedudecoction may have some therapeutic effect for resistant hypertension, its mechanism may be involved in ET decreasing and CGRP increasing.

Objective PSGL-1 is specifically expressed in leucocytes.The aim of this study was to explore the changes of myeloid-derived suppressor cells (MDSCs) in the spleen and bone marrow in PSGL-1-deficient mice.Methods PSGL-1 -/-mice were used in the experiment.After identification of the offsprings, flow cytometry was used to test the expression of CD11b and Gr-1 in C57 and PSGL-1 -/-mice.Results Compared with the C57 mice, the expression of MDSCs was up-regulated in the PSGL-1-deficient mice ( P <0.001).Conclusion The expression of MDSCs is upregulated in PSGl-1-deficient mice.

Objective To investigate the effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubi-cin-induced heart failure.Methods Male SD rats were randomly divided into sham operation group(sham group),model group, Xinkang group and captopril group.The rat model of heart failure was established by intraperitoneal injection of doxorubi-cin.Distilled water,Xinkang decoction and captopril were respectively administrated to rats by gavage for 35 d.The indexes of ventricular remodeling and cardiac function were measured.Myocardial fibrosis was assessed by Masson's trichrome stai-ning.The expression levels of collagen Ⅰ,collagen Ⅲ,TGF-β1,IκB and p56 were detected in myocardial tissues by Western blotting.Myocardial protein and mRNA levels of matrix metalloproteinase-2(MMP-2),MMP-9,and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)and TIMP-2 were detected by Western blotting and RT-qPCR,respectively.Results The expres-sion levels of collagenⅠand collagen Ⅲ protein,the collagen volume fraction(CVF),and the expression levels of TGF-β1 and p56 protein were significantly increased(P< 0.01),and the expression level of IκB protein was significantly decreased in the model group as compared with the sham group(P<0.05 for all).The myocardial protein and mRNA levels of MMP-2,MMP-9, TIMP-1,and TIMP-2 were significantly higher in the model group than in sham group(P<0.05 or P<0.01).The cardiac out-put(CO),left ventricular fractional shortening(FS),and left ventricular ejection fraction(LVEF)were significantly lower while the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),and left ventricular mass index (LVMI)were significantly higher in model group than in sham group(P<0.01).Compared with the model group,the expres-sion levels of collagen Ⅰand collagen Ⅲ protein,the CVF and the TGF-β1 and p56 expression levels were significantly decreased and the IκB protein expression was significantly increased in Xinkang and the captopril groups(P<0.05).The myocardial pro-tein and mRNA levels of MMP-2,MMP-9,TIMP-1,and TIMP-2 were significantly lower in Xinkang and captopril groups than in control group(P<0.05 or P<0.01).CO,FS,and LVEF were significantly higher while LVEDV,LVESV,and LVMI were significantly lower in Xinkang and captopril groups than in model group(P<0.01).Conclusion Xinkang recipe can reduce col-lagen deposition in the myocardia of rats with doxorubicin-induced heart failure,attenuate left ventricular remodeling,and im-prove cardiac function,which is associated with the inhibition of the NF-κB-mediated upregulation of TGF-β1.

ObjectiveTo investigate the effects of ulinastatin postconditioning and combining ulinastatin postconditioning with pretreatment on myocardial inflammatory response in patients undergoing cardiac valve replacement under CPB.MethodsEighty NYHA class Ⅱ or Ⅲ patients of both sexes aged 21-59 yr undergoing cardiac valve replacement under CPB were randomly divided into 4 groups ( n =20 each): group control (group C) ; group ulinastatin pretreatment ( group U1 ) ; group ulinastatin postconditioning (group U2 ) and group ulinastatin pretreatment and postconditioning combined (group U3 ).Ulinastatin 20 000 U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 after tracheal intubation until 10 min before cross-clamping of ascending aorta in groups U1 and U3.Ulinastatin 10 000 U/kg was infused into root of aorta at 4000-5000 U· kg- 1 · min- 1 at 5-7 min before declamping of aorta in groups U2 and U3.Blood samples were obtained from radial artery before cross clamping of ascending aorta,at 40 min after aortic cross-clamping,at 45 min after declamping of aorta (T3) and at the end of operation for polymorphonuclear leukocyte (PMN) count,routine analysis of blood and determination of plasma concentrations of IL-10,TNF-α,IL-1 and IL-6 (by ELISA).Myocardial specimens were obtained at 45 min after declamping of aorta for determination of IL-1β and IL-6 expression by immune-histochemistry.Results Ulinastatin pretreatment and/or postconditioning significantly increased plasma IL-10 concentration and decreased plasma IL-1,IL-6,TNF-α concentrations and PMN count and myocardial IL-1β and IL-6 expression in groups U1,U2 and U3 as compared with group C.Plasma IL-10 concentration was significantly higher and plasma IL-1,IL-6 and TNF-α concentrations,PMN count and myocardial IL-1β and IL-6 expression were lower in group U3 than in groups U1 and U2.ConclusionUlinastatin postconditioning can inhibit myocardial imflammatory response in patients undergoing valve replacement under CPB.The protective effect can be augmented by combining ulinastatin postconditioning with pretreatment.

Objective To evaluate the effects of ulinastatin on cardiac function in heart valve replacement patients with cardio-pulmonary bypass (CPB).Methods 120 patients received valve replacements were divided into 4 groups at random.Group U 1,preconditioning group:ulinastatin parenteral solution (20 000 U/kg) was injected into the central veins for 10 min before the ascending aorta was clamped.Group U2,postconditioning group:ulinastatin ( 10 000 U/kg) was injected into the aortic root for 5 min before the aortic clamp was opened.Group U3,combined the treatments of group U1 and group U2.Group C was served as control without using ulinastatin.The ST-T of ECG at different 8 time points was recorded from preanesthesia to the end of operation.The dosage of vasoactive agents in the 4 groups was recorded after the aortic clamp was opened.Blood samples were taken from the radial artery at 4 time points during 1O min before the ascending aorta was clamed to the end of operation for determining the serum concentration of H-FABP,IMA,CK-MB,MDA and SOD.The changes in myocardium were examined by microscope.Results The automatic reheating rate of heart in group U1,group U2,and group U3 were 70％,73％ and 90％ respectively,which were all higher than group C (33％) after the aortic clamp was opened in 3 -5 min.The scores of reperfusion arrhythmia,change of ST segments in ECG ( elevation or depression),the dosage of vasoactive drugs ( dopamine and adrenaline) and their using time,the concentration of MDA,H-FABP,IMA and CK-MB in group U1 and group U2 were ＜ than those of group C ( P ＜0.05 ),but was ＞ than those of group U3 ( P ＜0.05 ).The activity of SOD in group U1 and group U2 were ＞ than those of group C ( P ＜ 0.05 ),but was ＜ than those of group U3 ( P ＜ 0.05 ).There were no significant differences between group U1 and group U2( P ＞0.05 ).The myocardium in group C had focal coagulative necrosis.The damage of myocardium in group U3 was minor,the cytoplasm and nucleus was homogeneous,and the boundaries were distinct.Conclusion Ulinastatin parenteral solution preconditioning and postconditioning could improve heart function after valves replacement on CPB.The protective effects were not significantly different regarding ulinastati was administered into the central veins before the ascending aorta was clamped vs.it was injected into the aortic root before the aortic clamp opening.Combined these 2 administration methods and dosages could produce collaborative protection.