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The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.
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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.
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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.
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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.
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Objective To explore the therapeutic mechanism of kidney-reinforcing,blood-activating and phlegmresolving therapy for left ventricular fibrosis of spontaneously hypertensive rats (SHR).Methods Twenty SHR were randomly assigned to Chinese medicine group and model group.Additionally,ten Wistar-Kyoto(WKY) rats served as normal control group.After 12-week prevention,Masson staining method was used to measure the degree of fibrosis of left ventricular myocardial tissues,reverse transcription-polymerase chain reaction(RT-PCR) was used to detect Smad3 mRNA expression,and Western blotting method was used for the detection of Smad3 protein expression.Results The degree of left ventricular fibrosis myocardial tissue in Chinese medicine group was milder than that in the model group,and Samd3 protein and mRNA expression levels in Chinese medicine group were lower than those in the model group (P ＜ 0.05).Conclusion Kidney-reinforcing,blood-activating and phlegmresolving therapy can improve left ventricular fibrosis in SHR by inhibiting Smad3 expression.
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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 .
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Objective To investigate the syndrome types of traditional Chinese medicine ( TCM) in senile hypertension patients by cluster analysis. Methods Case report sheet for senile hypertension was formed, and then the general data and TCM syndrome information of 495 cases of senile hypertension were recorded. The frequency of syndrome information of the enrolled cases was analyzed, and then the syndrome types were classified by cluster analysis. Results The symptoms with high frequency in senile hypertension patients were dizziness ( 75.9%) , insomnia ( 33.1%) , chest distress ( 29.9%) , poor appetite ( 23.2%) , headache (22.4%), slippery pulse (54.9%), greasy fur (51.7%), stringy pulse (49.7%), and white fur (47.8%) . The main syndrome patterns of 495 cases of senile hypertension were upward hyperactivity of liver yang (23.8%), Qi deficiency and phlegm turbidity (21%), kidney qi deficiency (19.8%), phlegm blended with blood stasis (18.4%), and phlegm heat (17.0%) . Conclusion Senile hypertension patients are dominated with the syndrome types of upward hyperactivity of liver yang, Qi deficiency and kidney deficiency, and are usually complicated with phlegm turbidity, phlegm heat and blood stasis. The complicated syndromes of phlegm turbidity and blood stasis are commonly-seen. The results of cluster analysis are expected to supply evidence for the syndrome differentiation of senile hypertension.
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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.
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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.
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【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.
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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
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[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
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[Objective] To observe levels of plasma endothelin (ET) and calcitonin gene - related peptide (CGRP) in rats with myocardial hypertrophic heart failure affected by Yang Xin Kang (composed of Radix Ginseng, Radix Ophio-pogonis, Radix flicis Pubescetis, etc.) and its mechanism. [Methods] Rat models with myocardial hypertrophic heart failure was established by subcutaneous injection of isoprenaline for 13 days. Fifty rats were allocated to five groups: normal control (Group A), model (Group B), digoxin (Group C), high dosage of Yang Xin Kang (Group D) and low dosage of Yang Xin Kang (Group E). ET and CGRP levels were measured by radioimmunoassay method. [Results] ET level in Group B was higher and CGRP level lower than those in Group A (P
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Objective To compare the pathogenesis of coronary heart disease (CHD) with heart_blood stagnation syndrome (HBSS) due to Qi deficiency and Qi stagnation. Methods Indices such as endothelin,NO,TXB 2 ,6-Keto-PGF 1? ,blood rheology,platelet aggregation rate,atrial natriuretic factor,high_frequency electrocardiogram and cardiac function were observed. Results The changes of the above indices in CHD with HBSS due to Qi stagnation (Group A)were smaller than those due to Qi deficiency(Group B). Conclusion Qi stagnation is the primary stage of CHS with HBSS,the pathological changes being mild;Qi deficiency is the advanced stage,the pathological changes being severe.
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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.
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[Objective] To investigate the effect of Bao Xin Kang (BXK) on levels of cyclic adenosine monophosphate (cGMP) and cyclic guanosine monophosphate (cAMP) in vascular smooth muscle of rats with myocatdial hypertrophic heart failure and to explore its mechanism. [Methods] Fifty rats were randomly allocated to five groups: normal control group (Group A) , model group (Group B) , digoxin group (Group C), large - dose BXK group (Group D) and small - dose BXK group (Group E). Rat models with myocardial hypertrophic heart failure were established by subcutaneous injection of isoprenaline for 13 days. Radioimmunoassay was used to measure the levels of cAMP, cGMP and the ratio of cAMP/cGMP in vascular smooth muscle. The body weight and the weight of heart, liver and lung were measured and his-tomorphologic features of heart, liver and lung also examined. [Results] The levels of cAMP and cGMP and the heart index (heart weight /body weight) and the liver index (liver weight/body weight) in Group B were increased as compared with those in Group A (P
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[Objective] To observe the in-vitro inductive effect of ginsenosides (GS) on differentiation of rat bone marrow mesenchymal stem cells (MSC) into myocardial cells. [Methods] Marrow stromal cells were isolated from adult SD rats, and then were cultured and cloned by density gradient method and adhesive cultivation to prepare the primary MSC. The cell surface antigens of CD34 and CD44 were detected with flow cytometer to identify MSC. After subculture, the 8th generation of continuous MSC were induced by GS (250 mg/L) and 5-aza (5-azacytidine, 10 ?mol/L) and GS + 5-aza (250mg/L and 10 ?mol/L respectively) for 24, 48 and 72 hours to differentiate to myogenic cells. Meanwhile, a blank control group was set to compare the effect. After the induction, myocardial cell percentage was worked out after examining MSC count and positive cells count under the phase contrast microscope. The specific proteins of Desmin and cardiac troponin I (cTnI) in myocardial cells were detected by immunohistochemistry method, and the cardiac-specific gene expression of ?-MHC (myosin heavy chain) and ?-MHC in myocardiocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis. [Results] The cultured marrow stromal cells grew well, spindle in shape, and their CD44 expression was positive, indicating that marrow stromal cells differentiated to MSC. After induction with GS and 5-aza, MSC differentiated to myocardial cells, and the myocardial cell percentage was 38% in GS group, 35% in 5-aza group and 39% in GS + 5-aza group, the difference being insignificant. The expression of Desmin, cTnI and MHC in MSC was positive, and MSC were spindle-shaped and looked like fibroblast, indicating that MSC differentiated to myocardial cells. [Conclusion] Ginsenosides can induce MSC to differentiate to myogenic cells in-vitro, and this will supply evidence for cell transplantation.
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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.
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0.05). Conclusion Tianma Gouteng Decoction can reverse left ventricular hypertrophy and myocardial fibrosis,and its mechanism may be related to the inhibition of TGF-? 1 expression in cardiac muscle tissue.
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Objective To investigate the effect of Tianma Gouteng Decoction on myocardial fibrosis in renovascular hypertensive rat (RHR). Methods RHR models were established by occlusion of renal artery with artery forceps. The collagen concentration and the contents of collagen type I,III were measured. Meanwhile, the weight of heart and left ventricle was determined. Results (1)Both Tianma Gouteng Decoction and Captopril could reduce the left ventricle weight index (LVI) and collagen contents (P