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Objective: To observe the effect of phenylephrine (PE) on pressure overload induced myocardial ifbrosis (MF) with its relevance to transforming growth factor-β1 (TGF-β1), drosophila mothers against decapentaplegic protein 3 (smad3) and connective tissue growth factor (CTGF) signal pathway in experimental rats. Methods: A total of 28 male SD rats were randomly divided into 4 groups: Control group, AAC (abdominal aorta coarctation) group, AAC+PE group and AAC+prazosin group.n=7 in each group. Collagen volume fraction (CVF) of left ventricle was observed by myocardial collagen morphology, left ventricular myocardial tissue protein expressions of α-smooth muscle actin (α-SMA), TGF-β1, smad3 and CTGF were measured by immunohistochemistry, protein expression of α-SMA was also examined by Western blot analysis. Results:①Myocardial collagen morphology presented that compared with Control group, AAC, AAC+PE and AAC+prazosin groups had increased CVF, allP Conclusion: Phenylephrine could improve pressure overload induced MF in experimental rats which might be related to TGF-β1/smads signal pathway inhibition and CTGF down-regulation.
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Objective To study the expression of basic ifbroblast grouth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in different stages of myocardial ifbrosis (CFs). Methods CFs of neonatal Sprague-Dawley rats were isolated with the method of trypsin digestion and differential anchoring velocity, then cultured in vitro. The generation 2-4 of CFs were used for the experiment and randomly divided into 2 groups:the control group were cultured without AngII , and the test group were cultured with AngII 10-6 mol/L. The test group were cultured for 12, 24, 48, and 72 h respectively, and then the synthesis of col agen were measured by ELISA, the bFGF, TGF-β1-mRNA expression was measured by RT-PCR, and the bFGF and TGF-β1 protein expression was measured by western blot analyses. Results Compared with those of control group, the expressions of bFGF and TGF-β1 both in gene and in protein in the test groups increased gradual y with the timing (P?
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Objective: To observe the effects of astragaloside IV on myocardial fibrosis and connective tissue growth factor (CTGF) expression in experimental rats with chronic heart failure (CHF). Methods: CHF model was established by abdominal aorta constriction (AAC) and the rats were divided into 5 groups:Sham operation group, the rats received normal saline 2 ml/day, n=10, CHF group, the rats received normal saline 2 ml/day, n=12;Astragaloside IV groups, CHF rats received astragaloside IV at (20, 40, 60) mg/kg respectively and n=12 in each group. All animals were treated for 4 weeks. Hemodynamic indexes were monitored, left ventricular mass index (LVMI) was calculated, morphologic changes of myocardial tissue was observed by HE staining, myocardial ifbrosis degree and collagen volume fraction (CVF) were measured by Masson staining. The mRNA and protein expressions of CTGF were detected by RT-PCR and immunohistochemistry, Western-blot analysis respectivety. Results: Compared with CHF group, 3 Astragaloside IV groups had decreased LVMI and CVF, P Conclusion: Astragaloside IV can inhibit myocardial ifbrosis and improve cardiac function in CHF rats, which might be via inhibiting the over expression of myocardial CTGF.
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Objective: To investigate the impact and its possible mechanism of hydrogen sulfide (H2S) on myocardial collagen remodeling in experimental rats with diabetic mellitus (DM). Methods: Rat’s DM model was established by intraperitoneal injection of STZ at 40 mg/kg. A total of 40 SD rats were randomly divided into 4 groups:Control group, DM group, DM+NaHS group, in which NaHS worked as exogenous donor of H2S and NaHS control group. n=10 in each group, all animals were treated for 8 weeks. The cardiac collagen deposition was observed by Masson staining, protein expressions of cardiac collagen types I, III, IV and transforming growth factorβ1 (TGF-β1), connective tissue growth factor (CTGF) were examined by Western blot analysis. Results: Compared with Control group, DM group showed increased protein expressions of cardiac collagen types I and III, up-regulated expressions of TGF-β1 and CTGF, P Conclusion: H2S may improve the myocardial collagen remodeling in experimental DM rats, the mechanism might be related to the down-regulation of TGF-β1 and CTGF expression.
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Objective:To explicit phenylephrine (PE), α1-adrenergic receptor (α1-AR) on myocardial fibrosis regulation and interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α) expressions in pressure overloaded mice. Methods:A total of 49 KM mice were randomly divided into 3 groups: Blank control group, n=7, Sham operation group, n=7, Transverse abdominal aortic constriction (TAC) group, n=35, and 8 weeks later, the mice in TAC group were further divided into 5 sub-groups as TAC control, TAC+PE, TAC+Praz, TAC+Prop, TAC+Carv sub-groups, n=5 in each sub-group, and the animals were respectively treated for 3 weeks. Left ventricular collagen volume fraction (CVE), hydroxyproline content and IL-1, IL-6, TNF-α expressions were examined respectively. Results: By 8 weeks treatment, compared with Blank control group, TAC group had obvious myocardial fibrosis, increased hydroxyproline content and IL-1, IL-6, TNF-α expressions,P0.05; CVE and hydroxyproline content were similar between TAC+PE and TAC+Prop sub-groups, while the expressions of IL-1, IL-6 and TNF-α were obviously decreased in TAC+Prop sub-group,P<0.05. Conclusion: PE may improve myocardial ifbrosis and IL-1, IL-6, TNF-α expressions by activating α1-AR in pressure overloaded mice, α1-AR might be a defending factor for myocardial ifbrosis.
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Objective: To investigate the effects of Ala-Gln induced heat shock protein 70 (HSP70) expression on myocardial ifbrosis and connexin43 (Cx43) remodeling in experimental rats’ model. Methods: A total of 32 SPF male SD rats were randomly divided into 4 groups:①Control group,②Model group, the rats received isoprenaline (ISO) 5m/(kg·d),③Intervention group, the rats received ISO+Ala-Gln 0.75mg/(kg·d),④Quercetin group, the rats received ISO+quercetin 100mg/(kg·d)+Ala-Gln+DMSO. n=8 in each group. All animals were treated for 7 days and killed in 4 weeks for relevant examinations. HE and Masson staining was conducted to observe myocardial ifbrosis, then calculate collagen volume fraction; immunohistochemistry was applied to measure myocardial HSP70 expression, extracellular signal regulated kinase (p-ERK1/2) and Cx43 distribution, then conduct semi-quantitative analysis by speciifc soft ware. Results: HE and Masson staining indicated that Control group had no obvious myocardial ifbrosis, Model group and Quercetin group had obvious ifbrosis, and Intervention group showed less ifbrosis than the other 2 groups, all P0.05. The myocardial HSP70 expression was similar among Control, Model and Quercetin groups, P>0.05, while HSP70 expression was signiifcantly higher in Intervention group than the other 3 groups, all P Conclusion: Ala-Gln inducing the higher expression of HSP70, which may reduce myocardial ifbrosis in experimental rats, it could be because of HSP70 down regulating p-ERK1/2 expression and inhibiting ERK signaling pathway.
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s:Objective To investigate the possible role of basic ifbroblast growth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in mice with Coxsackie viral myocarditis and their relationship. Methods Eighty male BALB/c mice, 4 weeks old, were divided randomly into study group (n=40) and control group (n=40). The study group was repeated intraperitoneally injected with Coxasckie viral B3 to establish the model of viral myocarditis, while the control group was injected with virus-free Eagle’s medium in the same period. On the 7th, 14th, 28th and 42th day after the ifrst injection, 8 alive mice selected randomly from each group were sacriifced to examine the myocardial collagen volume fraction (CVF) by Masson dyeing, and to detect the protein and mRNA expression of bFGF and TGF-β1 by RT-PCR and immunohistochemistry. The correlations were analyzed. Results At each time point, the expressions of protein and mRNA of bFGF and TGF-β1 both in study group were signiifcantly higher than those in control group (P<0.01), and gradually increased over time. The expressions of protein and mRNA of bFGF and TGF-β1 were positively correlated with CVF (r=0.86~0.95, all P<0.01). In addition, the expressions of protein and mRNA of bFGF also had positive correlation with the expression of protein and mRNA of TGF-β1 (r=0.94, 0.92, P<0.01). Conclusion bFGF and TGF-β1 may promote the occurrence and development of myocardial ifbrosis in viral myocarditis, which may provide a new target for future treatment of myocardial ifbrosis.