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81.
糖尿病大鼠血、睾丸和脑组织内皮素水平的初步研究 总被引:1,自引:0,他引:1
目的 探讨糖尿病大鼠以及用银杏叶提取物 (EGb)治疗后血浆、睾丸和脑组织中内皮素的变化及意义。方法 将SD大鼠分为正常对照组、糖尿病模型组、EGb治疗组三组 ,在EGb治疗 5周后 ,用放射免疫法同时测定各组大鼠血浆、睾丸和脑组织中内皮素 (ET)的含量。结果 脑组织及血浆中ET含量正常对照组与糖尿病组比较无显著性差异 (P >0 0 5 ) ,睾丸组织中ET含量糖尿病组明显高于正常对照组 ,两者有显著性差异 (P <0 0 5 ) ;糖尿病组与EGb治疗组比较各种组织ET含量有下降倾向 ,但无显著性差异 (P >0 0 5 )。结论 糖尿病大鼠睾丸组织中ET含量增高 ,可能造成睾丸组织损害 ;EGb治疗可能有利于降低大鼠血液、睾丸和脑组织中的ET含量 ,但需进一步试验证实。 相似文献
82.
Miriam T Rademaker Chris J Charles Eric A Espiner Chris M Frampton John G Lainchbury A Mark Richards 《European heart journal》2005,26(19):2046-2054
AIMS: To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2). METHODS AND RESULTS: Eight sheep were administered the CRF-R2 antagonist CRF(9-41) (1.5 mg bolus) before (Normal) and after development of pacing-induced HF. Compared with controls, CRF(9-41) in HF significantly increased mean arterial pressure (MAP) (71+/-2 vs. 75+/-2 mmHg, P=0.0024) and calculated total peripheral resistance (CTPR) (33.3+/-5.2 vs. 39.4+/-5.9 mmHg/L/min, P=0.0455). Similar trends were observed in the Normal state (MAP 87+/-1 vs. 89+/-2 mmHg, P=0.0689; CTPR 21.9+/-2.0 vs. 24.4+/-2.4 mmHg/L/min, P=0.0731). Left atrial pressure was elevated similarly in both states (Normal P=0.0013; HF P=0.0298), whereas cardiac output tended to be reduced (Normal P=0.0614). CRF(9-41) increased plasma urocortin-I (Normal 10.3+/-0.8 vs. 19.8+/-1.3 pmol/L, P<0.001; HF 14.4+/-0.9 vs. 25.3+/-0.8 pmol/L, P<0.001), renin (Normal 0.34+/-0.06 vs. 0.41+/-0.02 nmol/L/hr, P=0.013; HF 1.14+/-0.29 vs. 1.57+/-0.36 nmol/L/hr, P=0.0326), aldosterone (Normal 370+/-62 vs. 563+/-99 pmol/L, P=0.0813; HF 662+/-141 vs. 1024+/-209 pmol/L, P=0.095), and endothelin-1 (HF 3.18+/-0.18 vs. 4.74+/-1.04 pmol/L, P=0.0087). MAP, CTPR, renin, and endothelin-1 responses to CRF-R2 antagonism were significantly greater in HF than in the Normal state (P=0.049, 0.0427, 0.0311, and 0.0412, respectively). CONCLUSION: These data suggest that the endogenous urocortin peptides contribute to the suppression of vascular tone and renin-angiotensin-aldosterone/endothelin activation in HF and thus, play a protective compensatory role in this disorder. 相似文献
83.
We describe characteristics of a selective endothelin (ET) ETB receptor antagonist, BQ‐788 [N‐cis‐2,6‐dimethylpiperidinocarbonyl‐L‐γ‐methylleucyl‐D‐1‐methoxycarbonyltryptophanyl‐D‐norleucine], which is widely used to demonstrate the role of endogenous or exogenous ETs in vitro and in vivo. In vitro, BQ‐788 potently and competitively inhibited 125I‐labeled ET‐1 binding to ETB receptors in human Girrardi heart cells (hGH) with an IC50 of 1.2 nM, but only poorly inhibited the binding to ETA receptors in human neuroblastoma cell line SK‐N‐MC cells (IC50, 1300 nM). In isolated rabbit pulmonary arteries, BQ‐788 showed no agonistic activity up to 10 μ and competitively inhibited the vasoconstriction induced by an ETB‐selective agonist (pA2, 8.4). BQ‐788 also inhibited several bioactivities of ET‐1, such as bronchoconstriction, cell proliferation, and clearance of perfused ET‐1. Thus, it is confirmed that BQ‐788 is a potent, selective ETB receptor antagonist. In vivo, in conscious rats, BQ‐788, 3 mg/kg/h, i.v., completely inhibited a pharmacological dose of ET‐1‐ or sarafotoxin6c (S6c) (0.5 nmol/kg, i.v.)‐induced ETB receptor‐mediated depressor, but not pressor responses. Furthermore, BQ‐788 markedly increased the plasma concentration of ET‐1, which is considered an index of potential ETB receptor blockade in vivo. In Dahl salt‐sensitive hypertensive (DS) rats, BQ‐788, 3 mg/kg/h, i.v., increased blood pressure by about 20 mm Hg. It is reported that BQ‐788 also inhibited ET‐1‐induced bronchoconstriction, tumor growth and lipopolysaccharide‐induced organ failure. These data suggest that BQ‐788 is a good tool for demonstrating the role of ET‐1 and ETB receptor subtypes in physiological and/or pathophysiological conditions. 相似文献
84.
《Critical reviews in oncology/hematology》2014,89(2):314-321
The endothelins and their associated receptors are important controllers of vascular growth, inflammation and vascular tone. In cancer, they have roles in the control of numerous factors in cancer development and progression, including angiogenesis, stromal reaction, epithelial mesenchymal transitions, apoptosis, invasion, metastases and drug resistance. Also, we consider current information on the role of this signalling system in cancer and examine the state of the current cell, animal and clinical trials utilizing endothelin targeted drugs for cancer management. Although targeting the endothelin axis in cell lines and xenografts show some promise in retarding cellular growth, results from limited clinical trials in prostatic cancer are less encouraging and did not offer significant survival benefit. The ability to target both cancer cells and vasculature via endothelin is an important consideration that necessitates the further refining of therapeutic strategies as we continue to explore the possibilities of the endothelin axis in cancer treatment. 相似文献
85.
Toshio Kaneda Zhi-Wei Zhang Tatsuya Ogawa Masaki Otaki Toshihiko Saga 《Scandinavian cardiovascular journal : SCJ》2013,47(2):105-107
Objective : Previous studies suggest that endothelin-1 (ET-1) plays a role in myocardial ischemia/reperfusion injury. Although administration of an endothelin receptor antagonist to the recipient has been shown to improve myocardial function after ischemia/reperfusion in a rat heart transplantation model, the effect of administering an endothelin receptor antagonist to the donor has not yet been examined. This study was designed to investigate the effects of pretreating donors with an ET A /ET B endothelin receptor antagonist (TAK-044) on myocardial function after cold preservation of a rat heart. Design : Male rats were pretreated with normal saline (control group, n = 8), TAK-044 (TAK group, n = 8, 1 mg/kg). Following cardiac arrest using cardioplegia, we washed out the coronary vascular beds with cold University of Wisconsin solution followed by 6-h preservation. After preservation, the hearts were mounted on a Langendorff apparatus to estimate aortic flow (AF), coronary flow (CF), cardiac output (CO), systolic pressure (SP), heart rate (HR), and rate-pressure product (RPP: HR 2 SP). The concentration of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) within the coronary perfusate during reperfusion was measured. Results : AF, SP, and CO were significantly greater in the TAK group than in the control group ( p = 0.0045, 0.004, and 0.0295, respectively). Conclusion : Pretreatment of donors with a nonselective endothelin receptor antagonist (TAK-044) improved cardiac functional recovery following preservation and may be beneficial for prolonged myocardial preservation. 相似文献
86.
Hanan M. El-Gowelli Maged W. Helmy Rabab M. Ali Mahmoud M. El-Mas 《Toxicology and applied pharmacology》2014
Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ETB receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β1, TGF-β1). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ETB receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ETB receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ETB receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. 相似文献
87.
目的探讨选择性逆向冠状静脉搭桥术对犬心肌缺血模型一氧化氮和内皮素的影响及其意义。方法16只健康成年杂种犬,随机分成缺血组(n=8)和选择性逆向冠状静脉搭桥组(n=8),观察不同时段两组血浆一氧化氮和内皮素含量的变化。并在选择性逆向冠状静脉搭桥组经静脉桥在体灌注墨汁,石蜡包埋后切片观察。结果后降支结扎前,两组血浆一氧化氮和内皮素含量无显著性差异(P>0.05),但结扎后两组血浆一氧化氮和内皮素含量在不同时段比较差异有统计学意义(P<0.01)。显微镜下,经静脉桥灌注的墨汁能在心肌组织间均匀分布。结论选择性逆向冠状静脉搭桥能使心肌得到有效灌注,通过维持犬心肌缺血模型血浆一氧化氮及内皮素水平,从而减轻心肌内皮细胞损害,保护心脏功能。 相似文献
88.
半边莲生物碱抑制肾性高血压大鼠内皮素1 mRNA和蛋白表达 总被引:1,自引:0,他引:1
目的观察半边莲生物碱对肾性高血压大鼠内皮素1 mRNA表达、蛋白合成和释放的影响。方法采用两肾一夹高血压大鼠模型,随机分为高血压组、半边莲组、卡托普利组和假手术组。用原位杂交技术观察大鼠外周血白细胞内皮素1 mRNA的表达,应用免疫组织化学染色计数大鼠主动脉内皮细胞铺片内皮素阳性细胞率(反映内皮素1蛋白的合成),用放射免疫技术测定大鼠血浆内皮素的含量。结果与假手术组比较,高血压组外周血白细胞内皮素1mRNA表达增强(34.64%±8.39%比9.34%±4.47%,P<0.05),动脉内皮细胞合成内皮素增多(7.42%±0.24%比1.58%±0.24%,P<0.05),血浆内皮素水平显著升高(221±24ng/L比138±19ng/L,P<0.05)。应用半边莲生物碱8周后,与高血压组比较,内皮素1 mRNA表达(20.38%±11.31%比34.64%±8.39%,P<0.05)、内皮素合成(3.53%±0.21%比7.42%±0.24%,P<0.05)和血浆内皮素水平(191±21ng/L比221±24ng/L,P<0.05)均受到显著抑制。结论肾性高血压大鼠伴有内皮素表达增强,半边莲生物碱能抑制内皮素基因的转录、蛋白合成及翻译,对防治肾性高血压所致的血管病变具有一定作用。 相似文献
89.
Krüger S Graf J Kunz D Stickel T Merx MW Hanrath P Janssens U 《European journal of heart failure》2005,7(4):475-478
BACKGROUND: Human Urotensin II (hU-II) is the most potent vasoconstrictor known to date. HU-II receptors are predominant in the human heart and arterial vessels, suggesting hU-II to be of importance as a cardiovascular mediator. METHODS: We studied 32 consecutive patients (60+/-12 years) with chronic heart failure (CHF) and 10 control subjects (54+/-12 years, n.s.) with cardiopulmonary exercise testing. Blood samples for the measurement of plasma hU-II and big-endothelin-1 (big-ET1) were obtained at rest and at peak exercise. RESULTS: Peak VO(2) was significantly higher in controls than in CHF patients (19.8+/-3.8 vs. 14.7+/-3.6 ml min(-1) kg(-1), P<0.001). Big-ET1 levels were increased in CHF compared to controls at rest (2.8+/-1.8 vs. 1.7+/-0.1 fmol/ml, P<0.01) and at peak exercise (2.7+/-1.7 vs. 1.6+/-0.2 fmol/ml, P<0.005). HU-II concentrations were comparable in patients with CHF and controls at rest (2990+/-1104 vs. 3290+/-508 pg/ml, n.s.) and peak exercise (3063+/-1185 vs. 3213+/-1188 pg/ml, n.s.). Resting hU-II levels demonstrated no correlation with peak VO(2) in controls or CHF patients. CONCLUSIONS: The measurement of circulating plasma levels of hU-II does not seem to be very helpful in studying the effects of hU-II in human cardiovascular regulation. A local paracrine or autocrine mediator effect of hU-II in CHF is possible. 相似文献
90.
慢性肺心病降钙素基因相关肽内皮素心钠素的表达及其临床意义 总被引:3,自引:0,他引:3
目的 :探讨降钙素基因相关肽 (CGRP)内皮素 (ET)心钠素 (ANP)在慢性阻塞性肺疾病肺心病病理生理过程所起的作用、临床意义及其相互关系。方法 :应用放射免疫方法测定单纯慢性支气管炎(A组 ) 2 1例 ,慢性支气管炎并阻塞性肺气肿 (B组 ) 2 7例 ,慢性支气管炎、阻塞性肺气肿并肺心病 (PHD)(C组 ) 3 2例及健康对照组 (D组 ) 2 4例CGRP、ET及ANP水平 ,同步测定动脉血气及第一秒用力呼气容积占预计值的百分比数 (FEV1 %P)。结果 :1 各指标变化 ( 1)CGRPB、C组急性期、稳定期均低于对照组 ,且急性期均低于稳定期 ;C组各期相应的低于B组 ,A组急性期、稳定期与对照组无明显差异 ;( 2 )ETA组急性期及B、C组急性期、稳定期均高于对照组 ,各自组急性期均高于稳定期 ,除A组稳定期降至正常外 ,B、C组稳定期均高于对照组 ,且C组各期相应的高于B组 ;( 3 )ANPB组急性期及C组急性期、稳定期均高于对照组 ,C组急性期明显高于B组急性期 ,B、C组急性期明显高于各自稳定期。 2 直线相关分析结果 :CGRP与PaO2 呈非常显著正相关 (P <0 0 1) ,与PaCO2 、ANP呈显著负相关 (P <0 0 5 ) ,与ET呈非常显著负相关 (P <0 0 1) ;ET与ANP非常显著正相关 (P <0 0 1) ,与PaCO2 正相关 (P <0 0 5 ) ,与PaO2 、FEV1 %P非常显著负相关 (P 相似文献