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Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.
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Objective: To investigate the protective effect of compound Longmaining isoprenaline hydrochloride-induced myocardial infarction model and its effect on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-kappa B (NF-κB) signaling pathway.Method: Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,compound salvia miltiorrhiza drop pill group (0.072 9 g·kg-1),and low,medium and high-dose compound Longmaining decoction groups (0.36,0.71,1.43 g·kg-1).The acute myocardial infarction model was induced through subcutaneous injection with isoproterenol.The pathological changes of myocardial tissue were examined by hematoxylin-eosin (HE) staining.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemotaxis protein-1(MCP-1) and nitrogen (NO) in serum were measured by enzyme linked immunosorbent assay (ELISA).The expression levels of inhibitors of NF-κB kinase subunit-β(IKKβ),NF-κB inhibitor α(IκBα),TLR4,MyD88 and NF-κB p65 were measured by immunohistochemical staining and Western blot.Result: Compared with normal group,the myocardial injury in model group was obvious.The levels of IL-1β,IL-6,TNF-α,MCP-1 and NO in serum increased significantly (PκBα decreased significantly (Pβ,TLR4,MyD88 and NF-κB p65 increased significantly in myocardial tissue (Pβ,IL-6,TNF-α,MCP-1 and NO levels in the serum (PκBα(Pβ,TLR4,MyD88 and NF-κB p65(PConclusion: Compound Longmaining plays a protective effect on acute myocardial infarction by regulatingthe expressions of TLR4/MyD88/NF-κB p65 signaling pathway and relevant inflammatory factors.
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Objective To investigate the effects of 2, 2, 6, 6-tetramethyl-4-piperidinol (tempol) on NF-κB signaling pathway of myocardial hypertrophy in rats. Methods The rat model of myocardial hypertrophy was established by intraperitoneal injection of isoprenaline (ISO) (5 mg/kg, twice per day, 2 weeks). A total of 42 male SD rats were randomly divided into 3 groups, including the control group, myocardial hypertrophy model group (ISO + sterile saline) and tempol treatment group (ISO + tempol) [tempol 100 mg/ (kg·d), 8 weeks]. Eight weeks after the corresponding drug intervention, the heart weight index (HWI) and left ventricular weight index (LVWI) were determined. Morphology and fibrosis of the myocardium were observed by HE staining, and the myocardial fibrosis of the rats was observed by Masson staining. The mRNA levels of TNF-α and IL-6 in the rat myocardial tissues were detected by qRT-PCR, and the expression levels of IκBα, p-p65 and p65 were detected by Western blot. Results Compared with the control group, the HWI and LVMI, mRNA levels of TNF-α and IL-6, and expression of p-p65/p65 in the model group were significantly increased (P＜ 0. 05), while the expression level of IκBα, an NF-κB inhibitory protein was significantly decreased (P＜0. 05). The pathological examination of the myocardial tissues showed thickening and disordered arrangement of myocardial fibers, and increased cross-sectional area of the myocardial fibers. The pathology by Masson staining showed aggravated myocardial fibrosis and increased collagen fibers in the myocardial interstitium. Compared with the model group, the HWI and LVMI, the mRNA levels of TNF-α and IL-6, and the expression of p- p65/p65 of the tempol group were significantly decreased (P＜ 0. 05), while the expression level of IκBα was significantly increased (P＜ 0. 05). HE staining showed that the degrees of myocardial disarrangement and cardiomyocyte hypertrophy were decreased. Meanwhile, Masson staining showed that the extent of myocardial fibrosis was reduced, and the interstitial collagen fibers were decreased. Conclusions Tempol can improve the isoprenaline-induced myocardial hypertrophy, which may be closely related with the inhibition of the activity of NF-κB signaling pathway.
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Objective:To investigate the protective effects and possible mechanisms of cortex phellodendri water extract and etha -nol extract on the myocardial injury induced by pituitrin and isoproterenol hydrochloride in rats .Methods:SD rats as the experimental animals were randomly divided into the normal control group , model group , compound Danshen tablets group , phellodendron water ex-tract group and phellodendron ethanol extract group .Pituitrin and isopropyl adrenaline hydrochloride were used to establish the myocar-dial injury model in rats.The serum CK, LDH activity, myocardial tissue SOD activity and MDA content were detected and compared . Results:Compared with those in the normal control group , the serum LDH activity , CK activity and MDA content were significantly in-creased , and the SOD activity in cardiac muscle and myocardial tissue was significantly decreased in the pituitrin -established myocardi-al injury model group (P<0.01).In the isopropyl adrenaline hydrochloride-established myocardial injury model group , the MDA con-tent in myocardial tissue was obviously increased , and the SOD activity in myocardial tissue was decreased obviously (P<0.01).The serum LDH activity, CK activity and MDA content were significantly decreased , and the SOD activity in cardiac muscle and myocardial tissue was increased significantly in all drug-taken groups when compared with those in the pituitrin-established myocardial injury model group, and the differences were statistically significant (P<0.05 or P<0.01).The MDA content in myocardial tissue was significant-ly reduced , and the SOD activity was increased significantly in all drug-taken groups when compared with those in the isopropyl adrena-line hydrochloride-established myocardial injury model group , and the differences were statistically significant (P<0.05 or P<0.01). Conclusion:Cortex phellodendri extract has certain protective effect on myocardial injury induced by pituitrin and isopropyl adrenaline hydrochloride in rats .
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Objective The purpose of the present study was to develop an animal model of type II diabetic coro-nary heart disease in Zuker diabetic fatty ( ZDF) rats.Methods The ZDF rat model of type II diabetic coronary heart disease was prepared by high-fat diet feeding combined with continuous injection of isoprenaline hydrochloride (ISO) in a dose of 1 mg· mL-1 for 10 consecutive days.Serum creatine kinase (CK), and creatine kinase izozyme (CK-MB), ST segment in electrocardiogram ( ECG) and myocardial pathological changes were detected to evaluate the rat model.Results CK of both the control and model groups was gradually increased with ISO injections, while CK-MB increased first and then decreased.The ST segment in ECG part II had significant changes.The pathological examination found that about half of the myocardial cross section in the model group was necrotic after injections of ISO for 5 days and more than 3/4 of the my-ocardial cross section was necrotic after injection of ISO for 10 days.The results indicated that ISO caused myocardial inju-ry in ZDF rats.Conclusions The variation of CK-MB, CK, ST segments in ECG and myocardial necrosis indicate that the model is successfully established.The use of high-fat diet combined with continuous injection of isoprenaline hydrochlo-ride in a dose of 1 mg· mL is a simple way to develop a Zuker diabetic fatty rat model of type II diabetic coronary heart dis-ease.
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Coleus forskohlii is an important ancient root drug of Indian origin, commonly known as gander in indian ayurvedic system of medicine. A lot of research work has been done on Coleus forskohlii regarding various cardiovascular disorders but no work has been done to find out its cardioprotective activity. Wistar albino rats were divided into five main groups having 5 animal each: Group 1 termed as Normal control (NC) received 0.5ml of normal saline throughout experimental period and served as control. Group 2 termed as Isoprenaline group (ISO) received 0.5ml of normal saline for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours. Group 3 termed as Standard group (STD) received Metoprolol (pure) (10 mg/kg/day, p.o.) for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours. Group 4 termed as Test group 1 (TG 1) & Group 5 termed as Test group 2 (TG 2) received Coleus forskohlii (50 mg/kg/day, p.o.) (100 mg/kg/day, p.o.) for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours respectively. The experiment was terminated on 31st day and animal were sacrificed by cervical decapitation after an overnight fast. Blood was collected for estimation of biochemical parameter and heart was dissected out for grading, heart/weight ratio and histopathological examination.the the level of marker enzyme in serum as AST, ALT, LDH, CK, Troponin-I were significantly decreased (P<0.001) in rats pretreated with Coleus forskohlii when compared to that of group which received isoprenaline alone. Further, histopathological examination showed the reduction of necrosis, edema and inflammation following Coleus forskohlii pretreatment. Based on present findings, it is concluded that Coleus forskohliil may be a potential preventive and therapeutic agent against the myocardial necrosis associated ischemic heart disease.
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Objective To study the influence of Captopril preconditioning on apoptosis and the expression of gp 130 in rats of acute myocardial injured. Method Wistar rats were randomly divided into three groups:control group, Iso group and Cap preconditioning group. Cardiomyocytes apoptosis was detected with TUNEL method. The expressions of Bcl-2 and Bax proteins in myocardium were tested by immunohistochemistry. The expression of gp 130 was tested with Western blot method. Results The index of cardiomyocytes apoptosis was decreased, the expressions of Bax proteins and gp 130 were decreased and the expression of Bcl-2 proteins was increased in Cap preconditioning group compared with Iso group (P<0.01 or P<0.05). Conclusion The expression of gp 130 could be decreased through Cap preconditioning, which can reduce the cardiomyocytes apoptosis.
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Aim To establish and evaluate a mouse model of my-ocardial fibrosis by hypodermic injection of isoprenaline. Meth-ods Kunming mice were randomly divided into 2 groups, namely, the myocardial fibrosis model group and the control group, 10 mice in each group. The mice in the model group were given isoprenaline 5 mg · kg-1 by hypodermic injection. From the following day, the dose of isoprenaline was reduced to 2. 5 mg·kg-1 , and lasted for 30 days. The mice in the control group were treated with the physiological saline in the same way. Final-ly, heart weight was then weighed and the cardiac weight index (CWI) was calculated. Hydroxyproline (Hydro) level in myo-cardium was determined by a colorimetric method. HE and Mas-son’s trichrome staining were used to estimate the extent of myo-cardial fibrosis and calculate the collagen volume fraction ( CVF) . RT-PCR was used to measure the myocardial Collagen I mRNA expression. Results Compared with the control group, the CWI and Hydro content in the myocardial tissues in the model group were increased(P<0.01). The content of col-lagen in the myocardial tissues and the CVF were increased obvi-ously(P<0.01). The RT-PCR results showed that the left ven-tricle Collagen I mRNA expression in the model group increased obviously( P<0.01 ) . Conclusion Isoprenaline-induced myo-cardial fibrosis model has been established and the method is very simple, economic and reliable.
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Objective To explore the inhibitory effect of calcitonin gene-related peptide (CGRP) on cardiomyocyte apoptosis and the underlying mechanism.Methods In cultured rat cardiomyocytes,apoptosis was induced by the incubation of isoprenaline ( 10ˉ5 mol/L) for 48 h.CGRP ( 10ˉ8 or 10ˉ7 mol/L) was administrated for 1 h before incubating isoprenaline to evaluate its effect on cardiomyocyte apoptosis.At the end of the drug treatment,the rate of apoptotic cells and intracellular reactive oxygen species (ROS) were determined,and RNA was extracted to examine the expression of microRNA-1 and microRNA-133a.Results Isoprenaline significantly increased the rate of apoptotic cells and intracellular ROS production concomitantly with the increased microRNA-1 expression and the decreased microRNA-133a expression,which were inhibited by pretreatment with CGRP.The effects of CGRP were reversed by CGRP receptor antagonist.Conclusion CGRP can inhibit the isoprenaline-induced cardiomyocyte apoptosis.The beneficial effect of CGRP is related to regulating microRNA-1 and microRNA-133a expression through the prevention of isoprenaline-induced ROS production.
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Objective To study the effect of granulocyte-macrophage colony-stimulating factor(GM-CSF)on angiogenesis of rat with acute myocardial injury induced by isoproterenol(Iso). Methods A total of 60 adult male Wistar rats were randomly divided into 3 groups: normal control group, GM-CSF pretreatment group (GM-CSF group), and lso injury group, 20 rats in each group. GM-CSF group was administered recombinant human(rh)GM-CSF(5.0 μg/kg), through tail intravenous injection once a day for three days. Then the GM-CSF group and the Iso injury group were anesthetized by intraperitoneal injection of lso( 15.0 mg/kg) once a day for three days. The same dose of saline was administered in the same way to the control rats. Ten days after injection, pathological changes of myocardial damage and infarct area were examined by immunohistochemistry. The mRNA expression levels of polypeptide antigen (CD34), vascular endothelial growth factor (VEGF) and its receptor KDR/flk- 1 were measured by RT-PCR. Results The difference of myocardial necrosis area between groups was statistically significant(F=10.07, P < 0.01), in which GM-CSF group[(37.37 ± 12.98)%] was significantly less than Iso injury group[(45.51 ±14.96)%, P < 0.05]. The difference of myocardial neovascularization density index of rats between groups was statistically significant ( F = 25.54, P < 0.05 ), in which GM-CSF group [(3980.05 ± 477.22) No/mm2] was significantly higher than Iso injury group((2605.93±361.49)No/mm2,P<0.01).The differences of myocardial CD34,VEGF,KDR/flk-1 mRNA expression between groups were statistically significant(F=17.83,4.29,4.10,all P<0.01).Compared to Iso mjury group[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01)]were higher in the GM-CSF group[CD34(44.04±10.13),VEGF(49A±11.59),and KDR/flk-1(46A9±7.90),all P<0.01].The expressions of myocardiM VEGF mRNA and its receptor KDR/flk-1 mRNA was positively correlated(r=0.725,R2=0.526,P<0.01).Conclusions GM-CSF prelreatmcnt increases the density ofnew blood vessels in myocardium,and reduces the Iso-induced myocardial injury in rats.
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Objective To study the protective effect of Huoxueyangyin granule on isoprenaline -induced acute myocardial ischemia in rats. Method The model was established by injecting isoprenaline. Results Huoxueyangyin Granule inhibited the increased locomotions of T wave and ST section of the abnormal ECG, decreased the level of LDH, protected myocardial SOD activity and reduced myocardial MDA production of isoprenaline-induced acute myocardial ischemia in rats. Conclusion Huoxueyangyin granule possesses protective effect on acute myocardial ischemia in rats.
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Objective:To study the protective e ect of Sini decoction on experimental myocardial ischemia in rats.Methods:The model of acute myocardial ischemia in rats was induced by subcutaneous injection of isoprenaline and sublingual venous injection of pituitrin.The changes of ECG,serum activity of creatine phosphokinase(CPK),lactate dehydrogenase(LDH),aspartate aminotransferase(AST),malondialdehyde(MDA) and superoxide dismutase(SOD)were measured.Results:Sini decoction signi cantly improved the extents of abnormal rising and lowering of ST segment(P
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Aim To investigate the effects of enalapril(Ena) on cardiac fibrosis induced by isoprenaline(Iso) and to explore its mechanism.Methods Effect of Ena and captopril(Cap) on collagen content,HW/BW,LVI,hydroxyprolnie(Hyp) level,and TGF-?1 protein expression was observed with IH and WB in rats induced by Iso subcutaneous injection.Results Different doses of Ena could decrease HW/BW,LVI and Hyp level dramatically,and decrease TGF-?1 protein expression which was closely related to myocardial fibrosis(MF).Conclusion Enalapril can inhibit TGF-?1 protein expression,by which inhibit myocardial fibrosis.
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Aim To further investigate the protective effect and mechanisms of total paeony glycoside (TPG) on apoptosis in experimental myocardial ischemic rats.Methods The myocardial ischemic model of rats was established by subcutaneous injection of isoprenaline (ISO), and early apoptosis rate of myocardial cells and the expression of apoptosis related genes Bax, Bcl-2 and proteins in myocardial tissues were analyzed and contrasted among five groups, including normal control, ISO injury, TPG prevention and treatment, TPG treatment and positive control.Results Compared with ISO injury group, all of indexes had improved in various degrees in TPG prevention and treatment group and TPG treatment group, such as the decrease of early apoptosis rate,expression of Bax gene and protein, the increase of Bcl-2 gene and protein and the ratio of Bcl-2 protein/Bax protein.Conclusion TPG has protective effect on apoptosis in ischemic myocardium induced by ISO.The pharmacological mechanism may relate to the activation of the Bcl-2 gene and protein expression, the inhibition of Bax gene and protein expression, as well as the increase of Bcl-2/Bax ratio.
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On the model of isoprenaline (ISO)-perinjured rat heart, the protctive effect of ischemic preconditioning (IPC) on ischemia reperfusion (I/R) damage was observed.It was found that compared with alone I/R group,IPC ameliorated I/R-induced reduced reduction of coronary blood flow (CBF) (8. 8 + 0. 6 vs 6. 6 + 0. 4mL/min,P
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The effect of fish oil on the basal left ventricular function and changes of left ventricular function induced by isoprenaline (ISO) was demonstrated in the study. The determination of cardiac performance in vivo showed that supplementation with fish oil (EPA and DMA,70%, 1. 4 mL/kg) had no significant effect on basal cardiac performance,while it could significantly inhibit the gains of +dp/dtmax,Vpm and HR induced by ISCK10 6 mol/L, 10 3 mol/L, 10 4 mol/L) introvenously. The result suggest that supplementation with fish oil have some effects on the function of B-adrenoceptors on rat myocardial membrane.
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Objective To evaluate the effects of aqueous extract from Semen Lepidii seu Descurainiae(SLD) on myocardial hypertrophy induced by isoprenaline(ISO) and L-thyroxine(L-Thy) in experimental mice and rats.Methods The myocardial hypertrophy models of mice were prepared by daily sc ISO 2 mg/kg for 7 d and of rats by daily ip L-Thy 0.3 mg/kg for 10 d.The mice were given aqueous extract from SLD 6 and 12 g/kg or Metoprolol 0.06 g/kg by ig administration once a day for 7 d,then the changes of cardiac indexes,plasma concentration of cAMP,and angiontensin Ⅱ(AngⅡ) content in myocardium were measured.The rats were given the aqueous extract from SLD 4 and 8 g/kg or Captopril 0.02 g/kg once a day for 10 d,then the changes of cardiac indexes,plasma concentration of ALD,AngⅡ content in left ventricle,and hydroxproline(Hyp) level were measured.Results Compared with the normal mice,cardiac indexs,plasma concentration of cAMP,and Ang Ⅱ content were remarkably increased in the model group(P
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Objective To observe the effect of Xin Guanxin Suhe Drop Pill(XGSDP) on isoprenaline (ISO)-induced acute myocardial ischemia (AMI).Methods Acute myocardial ischemia rats model were established by injection of ISO. Electrocardiogram (ECG) was observed, superoxide dismutase(SOD) activity, and the contents of malondialdehyde(MDA) and nitric oxide (NO) in the myocardial homogenate as well as serum and glutamate oxaloacetate transaminase (GOT) were observed after ISO injection. Results XGSDP could significantly increase NO content and SOD activity, decrease contents of MDA and GOT and reduce the positive rate of ECG( P
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Objective To observe the effects of cyclovirobuxinum D(Cvb-D)on the myocardium cell apoptosis of myocardial ischemia rats.Methods The rats were given Cvb-D 0.55,1.1 and 2.2 mg/kg orally per day for 21 days respectively.The myocardial ischemia model was induced by isoprenaline intraperitoneal injection.Myocardium tissue was observed under light microscope and end labelling TUNEL method was used to determine the cell apoptosis.Then the average percentage of apoptosis cell was figured out to evaluate the effect of Cyb-D.Results Cvb-D obviously lightened isoprenaline-induced myocardial pathological changes such as turbulence of myocardial fiber,plasmolysis of necrotic cell,inflammatory cell infiltration of necrotic interstitial region.Cvb-D remarkably inhibited myocardium cell apoptosis of myocardial ischemia rats caused by isoprenaline.Conclusion Cvb-D has the action of ameliorating myocardium cell apoptosis caused by myocardial ischemia.
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Objective To observe the effects of ginkgolides on hypoxia tolerance in mice and on myocardial ischemia injury in rats.Methods The mice were given isoprenaline 20 mg/kg(ip) and the survival time of the mice model under the hypoxic condition was recorded. Rat myocardial ischemia was induced by subcutaneous injection of over- dosage isoprenaline(8 mg/kg). Before modeling, rats were pretreated with ginkgolides 10, 20, 40 mg/kg, of ginkgo biloba( EGb) Extract 300 mg/kg, Propranolol 5 mg/kg,or vehicle for four days. The histological changes of myocardiim, serum creatine phosphokinase (CPK) level and lactate dehydrogenase (LDH) activity, myocardial lactate dehydrogenase(LDH) and superoxide dismutase (SOD) content were detected.Results Ginkgolides could prolong the survival time in the mice under a hypoxic condition, lessen the isoprenaline- induced rat myocardial ischemia, inhibit the activities of serum CPK and LDH and the increase of MDA content in ischemic myocardial tissue, enhance superoxide dismutase (SOD) activity. Conclusion Ginkgolides enhance to hypoxia the tolerance in mice and prevent rats from myocardial ischemic injury. The protective mechanism may be related to its inhibition of the activity of platelet activating factor and oxygen free radical.