OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs)...OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. RESULTS: Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P展开更多
OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, ...OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.展开更多
OBJECTIVE: To observe reversal of ventricular remodeling by the protein kinase C inhibitor Scutellarein in spontaneously hypertensive rats (SHRs). METHODS: Twelve SHRs were randomly divided into two groups. Scutellare...OBJECTIVE: To observe reversal of ventricular remodeling by the protein kinase C inhibitor Scutellarein in spontaneously hypertensive rats (SHRs). METHODS: Twelve SHRs were randomly divided into two groups. Scutellarein and saline (10 mg x kg(-1) x d(-1)) were given by intraperitoneal injection to two groups of rats separately. Systolic blood pressure (SBP) and ventricular weight index (LVW/BW, RVW/BW) were measured. A polarization microscope and an image analyzer system (IAS) were used to observe changes in cardiovascular structure and to count the content of cardiac muscle interstitial collagen. RESULTS: The pathologic changes in the left ventricle in the Scutellarein group rats (SHR(D)) improved to varying degrees, including hypertrophy of the cardiac muscle and collagen volume fraction. CONCLUSION: Scutellarein can reverse ventricular remodeling, improve myocardial stiffness and protect heart cardiac muscle.展开更多
OBJECTIVE: To evaluate the effects of Taichong(LR3) acupuncture points(acupoints) on the expression of glucose transporter protein 1(GLUT1) in the hypothalamus of spontaneously hypertensive rats(SHRs) as measured by c...OBJECTIVE: To evaluate the effects of Taichong(LR3) acupuncture points(acupoints) on the expression of glucose transporter protein 1(GLUT1) in the hypothalamus of spontaneously hypertensive rats(SHRs) as measured by combined positron emission tomography and computed tomography(PETCT).METHODS: Spontaneously hypertensive rats(SHR)were divided into model, Taichong(LR 3) acupuncture, and sham groups. Additionally, Tokyo Wistar rats were used as the control group. Changes in blood pressure were recorded in different groups of rats before and after the corresponding treatment. Hematoxylin and eosin(HE) staining was used to study basic morphological changes, and immunohistochemistry was used to determine GLUT1 expression in the hypothalamus. Further,PET-CT was utilized to elucidate the antihypertensive mechanism after acupuncture at the Taichong(LR 3) acupoints.RESULTS: PET-CT indicated activation of the hypothalamus. Measurement of blood pressure showed that acupuncture at the Taichong(LR 3) acupoints lowered blood pressure. HE staining did not show any significant pathological changes, although differences in cell number were observed. Immunohistochemical analysis indicated a GLUT1 downregulation in the SHRs of the Taichong(LR 3) acupuncture group after the treatment.CONCLUSION: Acupuncture at Taichong(LR 3) acupoints lowered blood pressure in SHRs, with possible mechanisms being changes in cell number and GLUT1 expression in the hypothalamus.展开更多
Background Tong-xin-luo capsule （TXL）, used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, i...Background Tong-xin-luo capsule （TXL）, used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats （SHR）. Methods Sixteen eight-week-old SHRs were randomized into an SHR group （n=8） and a TXL group （n=8） that were given Tong-xin-luo capsule （1.5 mg·kg^-1·d^-1）. Eight Wistar Kyoto （WKY） rats fed with 0.9% NaCl served as the control group （WKY group）. Systolic blood pressure （BP）, body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 （NF-κB P65） and peroxisome proliferators activated receptor y （PPAR-γ） protein and phosphorylated inhibitor kappa a （IκBα） protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IκBα and NF-κB were measured by co-immunoprecipitation. PPAR-γ mRNA, collagen Ⅰ mRNA and collagen Ⅲ mHNA were measured by real-time PCR.Results TXL inhibited NF-κB P65 expression and ventricular remodeling and suppressed the activation of NF-κB compared with the SHR group （P〈0.01, P〈0.05）. TXL reduced IκBα phosphorylation, increased expression of PPAR-γ protein and enhanced the physical interaction of the P65-P50 heterodimer with IκBα. The mRNA expression of PPAR-γ was enhanced but the mRNA expression of collagen Ⅰ mRNA and collagen Ⅲ mRNA were suppressed by TXL. Conclusions In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-γ that could result in the inhibition of the activation of NF-κB.展开更多
背景:原癌基因c-Src在调节高血压等心血管系统疾病中起着重要的作用,目前尚未看到有关运动干预影响主动脉血管内皮细胞c-Src的表达和活来调节高血压的研究。目的:观察有氧运动对自发性高血压大鼠主动脉血管内皮细胞c-Src m RNA表达和c-...背景:原癌基因c-Src在调节高血压等心血管系统疾病中起着重要的作用,目前尚未看到有关运动干预影响主动脉血管内皮细胞c-Src的表达和活来调节高血压的研究。目的:观察有氧运动对自发性高血压大鼠主动脉血管内皮细胞c-Src m RNA表达和c-Src活性的影响。方法:8只雄性Wistar大鼠作为正常对照组,16只自发性高血压大鼠随机分为自发性高血压组8只,自发性高血压运动组8只。自发性高血压运动组每天进行90 min无负重有氧游泳运动,6 d/周,共8周;正常对照组和自发性高血压组大鼠不做游泳运动。每周测定大鼠血压1次,8周后,测定各组大鼠主动脉血管内皮细胞c-Src m RNA表达和c-Src活性。结果与结论:与自发性高血压组相比,自发性高血压运动组血压明显降低,主动脉血管内皮细胞c-Src m RNA表达和c-Src活性明显升高。与正常对照组相比,自发性高血压运动组大鼠主动脉血管内皮细胞c-Src活性和c-Src m RNA表达高于正常对照组和自发性高血压组(P<0.01)。结果提示有氧运动可以促进自发性高血压大鼠主动脉血管内皮细胞c-Src活性和c-Src m RNA表达的增加。展开更多
文摘OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. RESULTS: Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P
基金ThisresearchworkwassupportedbyMinistryofPublicHealthandShanghaiBairenProjectFoundation (No .98BR0 3 8)
文摘OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.
文摘OBJECTIVE: To observe reversal of ventricular remodeling by the protein kinase C inhibitor Scutellarein in spontaneously hypertensive rats (SHRs). METHODS: Twelve SHRs were randomly divided into two groups. Scutellarein and saline (10 mg x kg(-1) x d(-1)) were given by intraperitoneal injection to two groups of rats separately. Systolic blood pressure (SBP) and ventricular weight index (LVW/BW, RVW/BW) were measured. A polarization microscope and an image analyzer system (IAS) were used to observe changes in cardiovascular structure and to count the content of cardiac muscle interstitial collagen. RESULTS: The pathologic changes in the left ventricle in the Scutellarein group rats (SHR(D)) improved to varying degrees, including hypertrophy of the cardiac muscle and collagen volume fraction. CONCLUSION: Scutellarein can reverse ventricular remodeling, improve myocardial stiffness and protect heart cardiac muscle.
基金National Key Basic Research Program of China(973 Program):Basic Research on the Specificity of the Meridian Effect and the Key Influencing Factors(No.2012CB518504)
文摘OBJECTIVE: To evaluate the effects of Taichong(LR3) acupuncture points(acupoints) on the expression of glucose transporter protein 1(GLUT1) in the hypothalamus of spontaneously hypertensive rats(SHRs) as measured by combined positron emission tomography and computed tomography(PETCT).METHODS: Spontaneously hypertensive rats(SHR)were divided into model, Taichong(LR 3) acupuncture, and sham groups. Additionally, Tokyo Wistar rats were used as the control group. Changes in blood pressure were recorded in different groups of rats before and after the corresponding treatment. Hematoxylin and eosin(HE) staining was used to study basic morphological changes, and immunohistochemistry was used to determine GLUT1 expression in the hypothalamus. Further,PET-CT was utilized to elucidate the antihypertensive mechanism after acupuncture at the Taichong(LR 3) acupoints.RESULTS: PET-CT indicated activation of the hypothalamus. Measurement of blood pressure showed that acupuncture at the Taichong(LR 3) acupoints lowered blood pressure. HE staining did not show any significant pathological changes, although differences in cell number were observed. Immunohistochemical analysis indicated a GLUT1 downregulation in the SHRs of the Taichong(LR 3) acupuncture group after the treatment.CONCLUSION: Acupuncture at Taichong(LR 3) acupoints lowered blood pressure in SHRs, with possible mechanisms being changes in cell number and GLUT1 expression in the hypothalamus.
文摘Background Tong-xin-luo capsule （TXL）, used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats （SHR）. Methods Sixteen eight-week-old SHRs were randomized into an SHR group （n=8） and a TXL group （n=8） that were given Tong-xin-luo capsule （1.5 mg·kg^-1·d^-1）. Eight Wistar Kyoto （WKY） rats fed with 0.9% NaCl served as the control group （WKY group）. Systolic blood pressure （BP）, body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 （NF-κB P65） and peroxisome proliferators activated receptor y （PPAR-γ） protein and phosphorylated inhibitor kappa a （IκBα） protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IκBα and NF-κB were measured by co-immunoprecipitation. PPAR-γ mRNA, collagen Ⅰ mRNA and collagen Ⅲ mHNA were measured by real-time PCR.Results TXL inhibited NF-κB P65 expression and ventricular remodeling and suppressed the activation of NF-κB compared with the SHR group （P〈0.01, P〈0.05）. TXL reduced IκBα phosphorylation, increased expression of PPAR-γ protein and enhanced the physical interaction of the P65-P50 heterodimer with IκBα. The mRNA expression of PPAR-γ was enhanced but the mRNA expression of collagen Ⅰ mRNA and collagen Ⅲ mRNA were suppressed by TXL. Conclusions In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-γ that could result in the inhibition of the activation of NF-κB.
基金The project supported by Provinicial Natural Science Foundation of Anhui Province(070413124)the Fresh Start Foundation of Wannan Medical College(BK00010804)~~
文摘背景:原癌基因c-Src在调节高血压等心血管系统疾病中起着重要的作用,目前尚未看到有关运动干预影响主动脉血管内皮细胞c-Src的表达和活来调节高血压的研究。目的:观察有氧运动对自发性高血压大鼠主动脉血管内皮细胞c-Src m RNA表达和c-Src活性的影响。方法:8只雄性Wistar大鼠作为正常对照组,16只自发性高血压大鼠随机分为自发性高血压组8只,自发性高血压运动组8只。自发性高血压运动组每天进行90 min无负重有氧游泳运动,6 d/周,共8周;正常对照组和自发性高血压组大鼠不做游泳运动。每周测定大鼠血压1次,8周后,测定各组大鼠主动脉血管内皮细胞c-Src m RNA表达和c-Src活性。结果与结论:与自发性高血压组相比,自发性高血压运动组血压明显降低,主动脉血管内皮细胞c-Src m RNA表达和c-Src活性明显升高。与正常对照组相比,自发性高血压运动组大鼠主动脉血管内皮细胞c-Src活性和c-Src m RNA表达高于正常对照组和自发性高血压组(P<0.01)。结果提示有氧运动可以促进自发性高血压大鼠主动脉血管内皮细胞c-Src活性和c-Src m RNA表达的增加。
