血管紧张素Ⅱ1型受体拮抗剂

摘要： 卵巢癌是女性生殖系统常见的恶性肿瘤之一,由于其发病隐匿,大多数患者出现症状就诊时已属晚期,且易发生转移和复发,死亡率居妇科恶性肿瘤的首位。因此进一步探究卵巢癌发生发展机制、寻找肿瘤潜在治疗靶点至关重要。血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)是肾素-血管紧张素系统(renin-angiotensin system,RAS)中最具生物活性的因子,主要参与机体血压和水盐代谢的调节,目前研究发现其与血管紧张素1型受体(angiotensin type 1 receptor,AT1R)结合激活相关通路与卵巢癌的发生、发展及转移过程密切相关,而AT1R拮抗剂(angiotensin receptor blocker,ARB)可以与AT1R选择性结合阻断AngⅡ-AT1R通路,从而阻断或抑制AngⅡ在卵巢癌中的作用。深入研究血管紧张素Ⅱ及其1型受体拮抗剂在卵巢癌中的作用机制或许能为寻找卵巢癌新的治疗靶点提供依据。

摘要： 目的 观察早期糖尿病肾病(diabetic nephropathy,DN)患者尿液中足细胞、足细胞相关蛋白nephrin、自噬基因Beclin-1 mRNA排泄及氯沙坦对上述指标的影响.方法 入选2018年1月-2021年1月我院确诊的符合标准的早期DN患者48例,给予氯沙坦50 mg或100 mg口服6个月,观察治疗前后患者尿液中微量白蛋白、足细胞、足细胞相关蛋白nephrin mRNA、自噬基因Beclin-1 mRNA排泄.结果 早期DN患者尿液中微量白蛋白排泄、足细胞及足细胞相关蛋白nephrin、自噬基因Beclin-1 mRNA排泄均较健康人明显增加(P<0.01).给予氯沙坦治疗6个月后,与治疗前比较,患者尿液中微量白蛋白、足细胞排泄减少(P<0.05),nephrin mRNA排泄呈下降趋势(P<0.05),自噬基因Beclin-1 mRNA排泄较治疗前有一定增加,但差异无统计学意义(P=0.067).结论 早期DN患者可通过尿液检查证实存在足细胞损伤.血管紧张素Ⅱ1型受体拮抗剂可以减少DN患者尿微量白蛋白排泄,保护足细胞,并可能增强足细胞自噬作用.

摘要： 目的 探讨双重肾素血管紧张素醛固酮系统(RAS)阻断剂治疗IgA肾病的临床疗效是否优于单用RAS阻断剂.方法 采用自身前后对照研究方法,回顾性研究就诊于本院门诊使用单独RAS阻断剂6个月后改用双重RAS阻断剂的IgA肾病患者病例资料,对比患者单独使用RAS阻断剂与使用双重RAS阻断剂的24 h尿蛋白定量变化情况,及血压、血肌酐、血钾等情况.结果 血管紧张素转化酶抑制剂(ACEI)联合血管紧张素Ⅱ受体阻断剂(ARB)治疗6个月后24 h尿蛋白定量明显低于单用ACEI/ARB治疗,ACEI联合ARB治疗6个月后24 h尿蛋白定量缓解率为60.23％,显著高于单独使用RAS阻断剂,经单用ACEL/ARB治疗及ACEI联合ARB治疗6个月后,患者收缩压及舒张压均较治疗前降低,差异有统计学意义(P＜0.05),血钾、血肌酐等指标较前未出现明显变化.结论 联合应用ACEI及ARB后24 h尿蛋白定量、尿蛋白缓解率高于单用ACEI/ARB,且具有安全性.

摘要： 目的 了解中西部城市老年急性心肌梗死(AMI)患者血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体拮抗剂(ARB)的使用情况及影响因素.方法 选择31家协作医院符合中国AMI治疗指南Ⅰ类推荐标准的患者1886例,其中2001年218例、2006年531例和2011年1137例,将服用ACEI/ARB患者为研究组1348例,未服用ACEI/ARB者为对照组538例.分析ACEI/ARB的使用情况及影响因素.结果 2组高血压、糖尿病、心力衰竭等比较,差异有统计学意义(P＜0.01).2001年、2006年和2011年患者ACEI/ARB使用率分别为74.3％、75.0％和69.3％(P=0.036).多因素分析显示,合并高血压、糖尿病、心力衰竭、入院时收缩压≥140 mm Hg(1 mm Hg=0.133 kPa)、未测量估算肾小球滤过率的患者更倾向使用ACEI/ARB,而女性、非前壁ST段抬高型心肌梗死、未测量LVEF、合并慢性肾功能不全的患者较少使用ACEI/ARB.结论 中西部城市老年AMI患者约1/3住院期间未接受ACEI/ARB治疗,且10年间无明显改善,该类药物的应用存在较大的改善空间.%Objective To study the application of ACEI/ARB in AMI patients from central and western cities of China and their influencing factors.Methods Collected clinical information of the elderly AMI patients in the year of 2001,2006 and 2011.A total of 1886 AMI patients were divded into ACEI/ARB treatment group (n=1348) and control group (n=538).The application of ACEI/ARB and their influencing factors were analyzed.Results The incidence of hypertension,diabetes mellitus and heart failure was significantly higher in ACEI/ARB treatment group than in control group (P＜0.01).The application rate of ACEI/ARB in 2001,2006 and 2011 was 74.3％,75.0％ and 69.3％ respectively (P=0.036).Multivariate logistic regression analysis showed that AMI patients with hypertension,diabetes,SBP≥ 140 mm Hg on admission,and unmeasured eGFR were more likely to receive ACEI/ARB treatment while female patients and those with nonanterior STEMI,unmeasured LVEF,and chronic renal insufficiency were less likely to receive ACEI/ARB treatment.Conclusion About one third of hospitalized elderly AMI patients from central and western cities of China do not receive ACEI/ARB treatment and have no significant improvement in the past 10 years.There is a large room for improving the application of ACEI/ARB in elderly AMI patients from central and western cities of China.

摘要： Fimasartan is a new angiotensin Ⅱ receptor antagonist.It was a derivative of losartan and provided higher potency and longer duration than losartan.Fimasartan was approved for the treatment of hypertension by the Korea Food and Drug Administration in 2010.This article summarized the pharmacodynamics,pharmacokinetics,clinical efficacy and adverse reactions of fimasartan.%非马沙坦为一新型血管紧张素Ⅱ受体拮抗药,为氯沙坦的衍生物,其降压作用较氯沙坦强,作用时间较氯沙坦持久.非马沙坦于2010年由韩国食品与药物管理局批准用于治疗高血压.本文从药效学、药动学、临床应用及不良反应等方面对非马沙坦进行了综述.

摘要： 目的 探究当归挥发油对自发性高血压大鼠(SHR)miR-155及其靶基因的影响,并从肾素-血管紧张素-醛固酮系统(RAAS)探讨当归挥发油对SHR血压的改善作用及其机制.方法 2015年10月—2016年4月,将8周龄48只SPF级雄性SHR随机分为模型组、当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组,各8只;另选取8只SPF级正常血压雄性Wistar大鼠作为正常组.正常组、模型组不给予任何药物,当归挥发油低剂量组、当归挥发油中剂量组、当归挥发油高剂量组、藁本内酯组、缬沙坦组大鼠分别灌胃给予当归挥发油乳剂12.6 mg·kg-1·d-1、37.0 mg·kg-1·d-1、100.0 mg·kg-1·d-1,藁本内酯溶液0.8 mg·kg-1·d-1,缬沙坦溶液51.4 mg·kg-1·d-1,连续给药4周,给药期间各组大鼠标准饮食、自由饮水.检测给药前及给药第1、2、3、4周各组大鼠收缩压变化.灌胃4周后处死大鼠取心脏,HE染色观察心肌组织病理学的变化,采用Western blotting法检测血管紧张素Ⅱ1型受体(AT1R)、细胞外调节蛋白激酶1/2(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)表达水平.采用RT-qPCR法检测miR-155表达水平.结果 不同处理情况、时间在大鼠收缩压中存在交互作用(P0.05).结论 当归挥发油能够明显抑制AT1R基因的表达,通过调节ERK1/2信号通路从而达到降压的功能;当归挥发油不通过miR-155在心肌组织发挥作用.%Objective To study the effect of angelica naphtha on the expression levels of miR - 155 and target genes in spontaneously hypertensive rats (SHR),and to investigate the influence and mechanism of action of angelica naphtha on lowering the blood pressure in SHR from the perspective of renin angiotensin aldosterone system (RAAS). Methods This study was conducted between October 2015 and April 2016. We randomized 48 SPF male SHR rats aged 8 weeks old into model group, low - dose angelica naphtha group,medium - dose angelica naphtha group,high - dose angelica naphtha group,ligustilide group,valsartan group with 8 SHR rats in each group,and selected 8 SPF male Wistar rats with normal blood pressure as the normal group. Low - dose angelica naphtha group,medium - dose angelica naphtha group,high - dose angelica naphtha group, ligustilide group,valsartan group were given intragastric administration of angelica naphtha emulsion 12. 6 mg·kg - 1 ·d - 1 , 37. 0 mg · kg - 1 · d - 1 ,100. 0 mg · kg - 1 · d - 1 ,ligustilide solution 0. 8 mg · kg - 1 · d - 1 ,valsartan solution 51. 4 mg·kg - 1 ·d - 1 ,respectively,once a day,for 4 weeks,while both the normal group and model group were not given any drugs during this period. All the groups had standard diet,and they could drink water freely during this period of intervention. Systolic blood pressure (SBP) was measured in each group before the intervention,at the 1st,2nd,3rd,and 4th weeks of intervention. All the rats were sacrificed and the heart was taken at the end of intervention. HE staining was used to recognize the morphologic changes in cardiac tissue. Western blotting was employed to determine the expression levels of angiotensin Ⅱ type 1 receptor (AT1R),extracellular signal - regulated kinase 1 / 2 (ERK1 / 2)and phosphorylated ERK 1 / 2 (p - ERK1 / 2). And RT - qPCR was adopted to measure the expression level of miR - 155. Results There was interaction on SBP in rats among different treatment ways and time (P 0. 05). Conclusion Angelica naphtha could significantly inhibit the expression of AT1R gene;by adjusting the ERK1 / 2 signaling pathway,it could lower the blood pressure;it did not affect the cardiac function via the expression of miR - 155.

摘要： Objective This study aims to investigate the relationship between the polymorphism of angiotensin Ⅱ type 1 receptor(AT1R) and the antihypertensive efficacy of telmisartan.Methods From June 2005 to January 2007,one hundred and forty-eight patients with mild-to-moderate primary hypertension were selected.All the patients accepted monotherapy of telmisartan for 8 weeks,blood pressure was measured 1-2 times/week.The AT1R genes 1166A/C,-810A/T and-521C/T polymorphism of the patients were analyzed by polymerase chain reaction (PCR).Some biochemical indexes such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(Cr),blood urea nitrogen(BUN),uric acid(UA),fasting plasma glucose (FPG),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),blood sodium,blood potassium,blood chloride,angiotensin Ⅱ(AngⅡ) were also measured at the same time.Results The body mass index(BMI),heart rate(HR),ALT,AST,Cr,BUN,UA,FPG,TC,TG,LDL-C,HDL-C,blood sodium,blood potassium and blood chlorine levels were compared before and after treatment,the differences were all not statistically significant(P>0.05).The AngⅡ level of the patients before and after treatment were compared,the difference was statistically significant(P0.05).The systolic blood pressure before and after treatment,systolic blood pressure drop,diastolic blood pressure before and after treatment between AT1R gene-521C/T CC genotype and CT+TT genotype were compared,there were no significant differences(P>0.05).The diastolic blood pressure drop was compared,there was a statistically significant difference(P0.05);患者治疗前后AngⅡ水平比较,差异有统计学意义(P0.05).AT1R基因-521C/T CC基因型、CT+TT基因型治疗前收缩压、治疗后收缩压、收缩压降幅、治疗前舒张压、治疗后舒张压比较,差异均无统计学意义(P>0.05);舒张压降幅比较,差异有统计学意义(P<0.05).多元线性回归分析结果显示,UA、-521C/T、治疗前AngⅡ、治疗前舒张压是影响舒张压降幅的因素(P<0.05).结论 AT1R基因-521C/T多态性能独立预测患者对替米沙坦反应的个体差异.

摘要： Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin Ⅱ type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography.Methods Pubmed,Embase,Cochrane library,Wanfang database and CNKI were searched.The literature limited range was from their start year to July 2015.Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed.Two investigators extracted data and performed quality analysis independently from all trims included.Rev man 5.3 software was used.Results 16 trials with a total of 15 897 patients were identified.There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group.The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35％ vs 12.13％,P=0.04,OR=1.44,95％CI 1.01-2.04).For patients with renal insufficiency,ACEI/ARB group had a higher CIN incidence than control group (12.23％ vs 7.32％,P=0.02,OR=1.80,95％CI 1.10-2.94),and the serum creatinine changes in ACEI/ARB group were higher than those in control group.There was statistical difference in serum creatinine changes between groups (P=0.02,MD=0.08,95％CI 0.02-0.15).Conclusions Renin-angiotensin system blockades can increase theincidence of CIN in patients undergoing angiography.Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.%目的 系统评价肾素-血管紧张素系统(RAS)阻滞剂对接受血管造影术患者发生造影剂肾病(CIN)的影响.方法 用计算机检索Pubmed、Embase、Cochrane图书馆、万方数据库和中国知网,检索时间从建库至2015年7月.纳入有关RAS阻滞剂影响CIN发生的随机对照试验(RCT)和非随机对照试验.由两名研究员分别对纳入研究进行数据提取和质量评价.用Rev man 5.3软件进行Meta分析.结果 共纳入9项随机对照研究和7项非随机对照研究,合计患者15 897例,其中7490例接受RAS阻滞剂治疗,对照组8407例.Meta分析结果显示,血管紧张素转化酶抑制剂(ACEI)/血管紧张素受体拮抗剂(ARB)组患者CIN的发生率高于对照组(14.35％比12.13％,P=0.04).对肾功能不全患者的进一步分析结果显示,ACEI/ARB组患者CIN发生率也高于对照组(12.23％比7.32％,P=0.02),且ACE/AARB组患者血管造影术后Scr升高绝对值大于对照组(P=0.02).结论 RAS阻滞剂可增加接受血管造影术患者的CIN发生率,RAS阻滞剂可促进肾功能不全患者CIN的发生.

摘要： 目的 探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)坎地沙坦对自发性高血压大鼠(SHR)骨骼肌胰岛素敏感性的影响及其机制.方法 30只SHR随机分为模型组、坎地沙坦高剂量组(Can 1组)及坎地沙坦低剂量组(Can 2组),每组10只,另选10只WKY大鼠作为对照组.均给予果糖喂养,Can 1组(0.8 mg/kg)、Can 2组(0.4 mg/kg)分别给予坎地沙坦灌胃干预,观察第8周末各组大鼠胰岛素抵抗指数(HOMA-IR)和AngⅡ的水平,以及骨骼肌蛋白激酶B(Akt)的基因及蛋白表达水平.结果 与对照组比较,模型组大鼠AngⅡ、HOMA-IR及血清空腹胰岛素(FINS)明显升高,骨骼肌中Akt mRNA表达及P-Akt蛋白表达显著减少,差异有统计学意义(P＜0.05,P＜0.01).与模型组比较,Can 1组大鼠FINS、HOMA-IR明显降低,Can 1组和Can 2组骨骼肌Akt mRNA表达及P-Akt表达显著增加,差异有统计学意义(P＜0.05,P＜0.01).结论 AngⅡ通过下调SHR骨骼肌的Akt蛋白表达引起胰岛素抵抗,而坎地沙坦通过抑制AngⅡ的这种作用改善骨骼肌胰岛素抵抗.

摘要： 本发明公开了一种血管紧张素II受体2(AT2R)拮抗剂的盐型、晶型及其制备方法，还包括所述盐型和晶型在制备治疗慢性疼痛药物中的应用。

摘要： 本发明涉及医药技术领域，特别是涉及提供血管紧张素Ⅱ1型受体拮抗剂在制备预防、治疗血小板减少症产品中的用途；其中，血小板减少症为脓毒症并发血小板减少症；血管紧张素Ⅱ1型受体拮抗剂为氯沙坦钾、坎地沙坦、替米沙坦、缬沙坦、依普沙坦、伊贝沙坦中的一种或几种。本发明的血管紧张素Ⅱ1型受体拮抗剂尤其是氯沙坦钾是用于治疗高血压的老药，其制备技术成熟，因此可以很方便的从市场获得商品化制剂，使其用在制备预防、治疗血小板减少症产品中，且血管紧张素Ⅱ1型受体拮抗剂给药方法简单方便、起效迅速。

摘要： 本发明公开了一种血管紧张素受体拮抗剂和中性内肽酶抑制剂的超分子复合体的新晶型。本发明公开的该超分子复合体的新晶型，其水溶性高、稳定性好。实验表明，其吸湿性和固有溶出程度和速度均优于已有的超分子复合体晶型。

摘要： 本发明涉及含有至少一种加压素受体拮抗剂和至少一种血管紧张素受体阻滞剂(ARB)的某些药物组合物和用于制备这些化合物、它们的组合物、中间体及衍生物的方法以及用于治疗加压素和/或血管紧张素介导的疾病的方法。

摘要： 本公开涉及血管紧张素II受体及内皮素受体双重拮抗剂。具体而言，本公开提供了式I所示化合物及其制备方法。该化合物可用于治疗高血压或肾病等疾病。

摘要： 本发明涉及医药技术领域，特别是涉及提供血管紧张素Ⅱ1型受体拮抗剂在制备预防、治疗血小板减少症产品中的用途；其中，血小板减少症为脓毒症并发血小板减少症；血管紧张素Ⅱ1型受体拮抗剂为氯沙坦钾、坎地沙坦、替米沙坦、缬沙坦、依普沙坦、伊贝沙坦中的一种或几种。本发明的血管紧张素Ⅱ1型受体拮抗剂尤其是氯沙坦钾是用于治疗高血压的老药，其制备技术成熟，因此可以很方便的从市场获得商品化制剂，使其用在制备预防、治疗血小板减少症产品中，且血管紧张素Ⅱ1型受体拮抗剂给药方法简单方便、起效迅速。

摘要： 本发明涉及一种最新一代抗心衰药物缬沙坦((2R，4S)-5-联苯-4-基-5-(3-羧基-丙酰基氨基)-2-甲基-戊酸乙酯)三钠的无定型晶型及其制备方法。

摘要： 本发明公开了一种血管紧张素受体拮抗剂和中性内肽酶抑制剂的超分子复合体的新晶型。本发明公开的该超分子复合体的新晶型，其水溶性高、稳定性好。实验表明，其吸湿性和固有溶出程度和速度均优于已有的超分子复合体晶型。

摘要： 本发明属于医药技术领域，涉及血管紧张素II的I型受体拮抗剂在促进毛发生长方面的新用途。本发明创造性的发现血管紧张素II的I型受体拮抗剂具有良好的促进毛发生长的作用，并通过研究表明其促进毛发生长的作用机理为：利用血管紧张素II的I型受体拮抗剂可以刺激缓激肽B2受体引起内源性的前列腺素F-2a的释放，通过前列腺素的受体途径改善局部微环境促进毛发生长；同时血管紧张素II的I型受体拮抗剂还能有效的阻断血管紧张素II的作用，促进局部血液的供给，从而达到促进毛发生长的效果。本发明为多靶点药物的研发提供了很好的理论依据，为治疗各种脱发的药物研发提供了新的方向。

摘要： 本发明公开了一种新型氨基酸联苯化合物，该化合物是由联苯与氨基酸、噁二唑有机地连接起来而成，是血管紧张素II的1型受体拮抗剂，该化合物可用于制备预防或治疗高血压、冠心病、心脑肾血管疾病、偏头痛、肺动脉高压等疾病的药物，也可以有效地抑制原位癌，如胃癌、胰腺癌、卵巢癌、前列腺癌、肺癌、膀胱癌、肝癌、肾癌、乳腺癌、宫颈癌、结肠癌等的增殖、迁移。