哮喘小鼠肺脏组织肾素-血管紧张素系统相关组分表达 及AT1R拮抗剂对其影响

目的：探讨肾素-血管紧张素系统（RAS）与哮喘发生的关系,为哮喘发病机制的研究和治疗提供理论依据。方法：复制小鼠哮喘模型,小鼠分为对照组、模型组、坎地沙坦低剂量组及高剂量组,采集小鼠血清,测量血清中血管紧张素Ⅱ (AngⅡ)与血管紧张素Ⅰ(AngⅠ)的含量;通过Western blotting和RT-PCR观察RAS中血管紧张素原(AGT)、血管紧张素转换酶(ACE)、血管紧张素Ⅱ 1型受体（AT₁R）和2型受体（AT₂R）在各组小鼠肺组织中的表达。结果：模型组小鼠血清AngⅡ含量较对照组增高（P<0.05）,坎地沙坦组与模型组比较无明显变化（P>0.05）。各组小鼠血清中AngⅠ含量比较差异无统计学意义（P>0.05）。模型组小鼠AT1R和ACE蛋白表达较对照组明显增加（P<0.05）,坎地沙坦组AT₁R表达与模型组比较明显降低(P<0.05),ACE无明显变化（P>0.05）。AT₂R蛋白表达各组间比较差异无统计学意义（P>0.05）。模型组小鼠ACE mRNA表达较对照组明显增加（P<0.05）,坎地沙坦组与模型组比较差异无统计学意义（P>0.05）。模型组小鼠AT1R mRNA表达较对照组明显增加（P<0.05）,坎地沙坦组较模型组明显降低（P<0.05）。模型组AT2R mRNA较对照组明显降低（P<0.05）,坎地沙坦组较模型组明显增加（P<0.05）。各组AGT mRNA表达无明显变化（P>0.05）。  结论：在小鼠哮喘发病过程中,RAS活化参与了哮喘的发病过程,并且AT₁R拮抗剂坎地沙坦可以逆转ACE、AT₁R和AT₂R表达的改变。     

血管紧张素转化酶2与心脏疾病

肾素-血管紧张素系统（renin—angiotensin system，RAS）是机体重要的体液调节系统，作用于RAS和血管紧张素转化酶（angiotensin—convertinq enzyme，ACE）可将无活性的血管紧张素Ⅰ（angiotensinⅠ，AngⅠ）转化为血管收缩活性很强的血管紧张素Ⅱ（angiotensinⅡ，AngⅡ），并可灭活具有血管扩张效应的缓激肽。AngⅡ通过血管紧张素受体（angiotensinⅡ receptor type1，AT1和angiotensin Ⅱ receptor type 2，AT2）介导许多生理病理反应。     

血管紧张素Ⅱ拮抗剂的肾损害

血管紧张素Ⅱ（AngⅡ）拮抗剂包括血管紧张素转换酶抑制剂（angiotensin converting enzyme inhibitor，ACEI）和血管紧张素AT1受体阻断剂（angiotensin AT1 receptor blocker，ARB）两类。它们都是治疗高血压的重要药物。ACEI能阻断血管AngⅡ生成，ARB能阻断AngⅡ与AT1受体结合，都能拮抗AngⅡ的致病作用，降低高血压并发挥肾脏保护效应。     

幼年大鼠交感神经损伤后血管紧张素受体功能及表达的变化

目的观察交感神经损毁对大鼠血管紧张素受体的功能与表达水平的影响。方法6-羟多巴胺（6-hydroxydopamine,6-OHDA）损毁新生雄性Wistar大鼠的交感神经末梢,11周后检测下列指标：①血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）升血压和缩血管的作用,②心肌AngⅡ1型受体（angiotensin Ⅱtype 1 receptor,AT1R）与[^3H]-AngⅡ的亲和力,③血管平滑肌AT1R mRNA的表达水平。结果幼年损毁大鼠交感神经,大鼠成年后AngⅡ引起的升血压和缩血管作用显著增强,血管平滑肌AT1R mRNA表达水平升高,心肌AT1R饱和曲线明显上升,受体数量（Bmax）增加,亲和指数（KD）未发生明显变化。结论幼年损毁大鼠交感神经,可使血管平滑肌AT1R表达增强,进而导致AngⅡ引起的升高血压和收缩血管作用显著增强,这可能是幼年损毁交感神经后大鼠维持正常血压心率的重要原因之一。     

血管紧张素Ⅱ受体拮抗剂与心肌梗死的争议和进展

血管紧张素转换酶抑制剂（angiotensin converting enzyme inhibitor，ACEI）已广泛应用于治疗心血管疾病，成为高血压、充血性心力衰竭和心肌梗死（myocardial infarction，MI）的常规用药。多个大型临床试验已证实ACEI可以降低心血管疾病患者的发病率和病死率。从理论上说，血管紧张素受体拮抗剂（angiotensin receptor blockers，ARBs）可以更直接、有效地抑制体内各种途径产生的血管紧张素Ⅱ（angiotensin Ⅱ，AngⅡ），其临床效果应强于ACEI。但是，最近的临床试验结果并没有显示出ARB的优越性，相反，有研究报道ARB可能增加心肌梗死的发病率和病死率心。该发现引起了医学界和患者的广泛关注。本文就血管紧张素Ⅱ受体拮抗剂是否增加心肌梗死发病率和病死率及其相关机制进行简要综述。     

血管紧张素及其受体对纤溶系统的调节作用与临床意义的研究

纤溶系统在高血压、动脉粥样硬化、心肌梗死等心血管疾病的发生、发展过程中具有重要的作用.肾素-血管紧张素系统(renin-angiotensin system,RAS)与纤溶系统之间存在着十分密切的相互作用[1],RAS是纤溶功能强有力的调节者.近年来,血管紧张素(angiotensin,Ang)及其受体对纤溶系统的作用以及血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitor,ACEI)和AngⅡⅠ型(AT1)受体拮抗剂对纤溶系统影响的研究取得了一些进展,本文将就这方面的内容作一简要综述.     

血管紧张素Ⅱ1型受体基因多态性与高血压患者伊贝沙坦降压疗效的关系

高血压发病机制复杂,同时个体之间存在明显的药效个体差异,使临床降压药物的选择存在一定的盲目性.如何为患者选择合适的降压药物,进行个体化治疗,已成为高血压治疗中的难点.肾素-血管紧张素系统(renin-angiotensin system ,RAS)在人体血压调控中起着重要的作用,已有研究显示血管紧张素Ⅱ1型受体(angiotensin Ⅱ type 1 receptor,AT1R)基因上的多态性位点1166 A/C可能与高血压发病有关[1].AT1R作为血管紧张素Ⅱ受体拮抗剂(angiotensin Ⅱ receptor blocker,ARB)的作用靶点,其基因变异是否在ARB类药物药效个体差异的产生中发挥作用国内外有关报道较少.     

血管紧张素Ⅱ致心肌纤维化及其信号转导机制研究进展

心脏重构包括心脏肥厚和心肌纤维化（myocardial fibrosis,MF）两个方面,MF主要是在各种病理生理因素作用下,心脏局部的成纤维细胞过度增殖,细胞外基质沉积及Ⅰ、Ⅲ型胶原不成比例增加.肾素-血管紧张素-醛固酮系统（reninangiotensin-aldosterone eystem,RAAS）是心肌纤维化过程中重要的神经内分泌机制之一,血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）是RAAS最重要的效应因子,不仅来源于经典的RAAS,还可由心脏局部的心肌细胞和成纤维细胞合成释放,以旁分泌或自分泌的方式发挥生物学效应.AngⅡ致心肌纤维化的信号通路复杂,主要通过与其特异性受体AngⅡ1型受体（angiotensinⅡtype 1 receptor,AT1R）结合,并激活一系列信号分子通路将细胞外信号传递至细胞内产生纤维化效应.     

妊娠期高血压疾病患者血管紧张素Ⅱ1型受体基因多态性

目的：探讨血管紧张素Ⅱ 1型受体(AT₁R) 基因非编码区（-535）位点多态性与妊娠期高血压疾病（HDCP）发病的关系。方法：采用聚合酶链反应-限制性酶切片段长度多态性（PCR-RFLP）技术检测86例HDCP组孕妇（妊娠期高血压17例、子痫前期轻度28例、子痫前期重度23例、子痫18例）和74例对照组（正常孕妇)基因型。结果：①HDCP组孕妇AT₁R 基因（-535）位点基因型CC、CT、TT频率分别为74.4%、20.9%和4.7%,对照组分别为87.8%、8.1%和4.1%,两组基因型频数分布比较差异无显著性（P>0.05）;HDCP组孕妇AT₁R 基因（-535）位点等位基因C、T频率分别为84.9%和15.1%,对照组分别为91.9%和8.1%,两组等位基因频率比较差异亦无显著性（P>0.05）;②HDCP组妊娠期高血压、子痫前期轻度、子痫前期重度和子痫孕妇（-535）位点T等位基因频率分别为5.9%、7.1%、15.2%和36.1%,前3者与子痫患者比较差异均有显著性（P<0.05）。结论：AT₁R基因（—535）C→T变异与妊娠期高血压疾病发病无关,但与病情严重程度有关     

血管紧张素II受体拮抗剂坎地沙坦应用的研究进展

肾素-血管紧张素-醛固酮系统包括了肾素、血管紧张素I、血管紧张素II(AngII)、醛固酮等,AngII是该系统中重要的活性物质,通过与受体结合而发挥作用。坎地沙坦是一种新型的血管紧张素II受体拮抗剂(angiotensin receptorl receptorbloker,ARB),由于非竞争性的与AT1受体结合的独特     

Macrophage exosomes transfer angiotensin II type 1 receptor to lung fibroblasts mediating bleomycin-induced pulmonary fibrosis

Background:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student''s t test or analysis of variance were used for statistical analysis.Results:In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production.Conclusions:Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.     

柚皮素抑制马凡综合征小鼠胸主动脉瘤的形成

目的：探究柚皮素对马凡综合征胸主动脉瘤的作用。方法：对马凡综合征模型Fbn1^C1039G/+小鼠进行柚皮素灌胃,观察柚皮素对小鼠胸主动脉瘤形成的影响,并在体外利用生物荧光共振能量转移、原子力显微镜、同位素标记配体-受体结合等技术探究柚皮素发挥作用的分子机制。结果：Fbn1^C1039G/+小鼠予以柚皮素长期预防性给药(6～26周)或治疗性给药(20～26周)均显著抑制小鼠胸主动脉瘤的扩张和弹力板的断裂。同时,柚皮素喂养可降低小鼠血管壁Smad2和细胞外调节蛋白激酶1/2(extracellular regulating kinase 1/2,ERK1/2)的磷酸化以及基质金属蛋白酶(matrix metalloproteinase, MMP)2/9的表达与活性。机制上,柚皮素处理降低血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)受体1(angiotensinⅡtype 1 receptor, AT1)下游Gq蛋白介导的蛋白激酶C(protein kinase C,PKC)和ERK1/2的磷酸化、钙离子信号和活化T细胞核因子(nuclear ...     

Involvement of Ca^2＋-activated K^＋Channels in Receptor-Regulated Sperm Motility in Rats

Ion fluxes have been implicated in sperm functions.A pivotal role of Ca2 hasbeen observed in variousreproductive events including sperm capacitation,acrosomereaction[1～ 3] ,sperm activation[4～ 5] and sperm motility[6～ 8] .The importance of Ca2 in-f…     

大鼠延髓头端腹外侧部微量灌注血管紧张素Ⅱ对压力感受性反射敏感性的影响

目的 :探讨延髓头端腹外侧部 (RVLM )血管紧张素Ⅱ和血管紧张素Ⅰ型 (AT1 )受体阻断剂losartan对大鼠压力感受性反射敏感性的影响。方法 :试验采用 2 3只乌拉坦麻醉的正常大鼠 ,静脉注射不同剂量的苯肾上腺素 (1,5 ,10 ,2 0 ,4 0 μg kg)升高血压而诱发动脉压力感受性反射 ,观察RVLM微量灌注AngⅡ和losartan对压力感受性反射敏感性的影响。对不同剂量苯肾上腺素引起的平均动脉压变化和对应的心率反射性变化进行直线回归分析 ,以直线斜率反映动脉压力感受性反射敏感性。结果 :RVLM注射AngⅡ引起压力感受性反射敏感性显著降低 ,losartan对压力感受性反射敏感性虽无直接影响 ,但可消除AngⅡ的降低压力感受性反射敏感性效应。结论 :RVLM的外源性AngⅡ可降低压力感受性反射敏感性 ,其作用是由AT1 受体介导的。RV LM的AT1 受体不参与压力感受性反射敏感性的紧张性调节作用。     

Interaction of signal transduction between angiotensin AT1 and AT2 receptor subtypes in rat senescent heart

Background  Angiotensin II (Ang II) acting at angiotensin AT₁ receptor (AT₁R) has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, which are believed to be opposed by angiotensin AT₂ receptor (AT₂R) stimulation. The expressions of AT₁R and AT₂R are up-regulated in senescent hearts. The purpose of this study was to investigate the interaction of signal transduction between AT₁R and AT₂R, and to detect whether there is any difference in the interaction in rat hearts of different age.
Methods  In 3.5-, 12-, 18- and 24-month-old rats, the heart cell membrane activities of protein kinase C (PKC) and tyrosine kinase were measured when AT₁R and AT₂R were both activated by Ang II or just the AT₁R was activated by Ang II and PD123319. The activities of cytosolic phospholipase A₂ (cPLA₂) and the levels of cGMP were investigated when AT₁R and AT₂R were both activated by Ang II or just the AT₂R was activated by Ang II and losartan. 
Results  When AT₁R and AT₂R were both activated compared to when the AT₁R was activated, the activities of PKC were not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; the activities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. The activities of cPLA₂ were all decreased significantly in rats of different age when AT₁R and AT₂R were both activated compared to when the AT₂R was activated. Treatment with Ang II alone compared to Ang II and losartan decreased the levels of cGMP (fmol/mg) in rats of different age (102.7±12.7 versus 86.0±8.0 in 3.5-month-old rats, P<0.05; 81.0±9.4 versus 70.0±6.3 in 12-month-old rats, P<0.05; 69.8±5.6 versus 54.2±5.3 in 18-month-old rats, P<0.01; 57.7±8.0 versus 39.0±3.0 in 24-month-old rats, P<0.01).
Conclusions  The activation of AT₁R inhibited the signal transduction of AT₂R during the aging variation, and the activation of AT₂R inhibited the signal transduction of AT₁R in rat heart of different age.

     

Effect of angiotensin Ⅱ and angiotensin Ⅱ type 1 receptor antagonist on the proliferation,contraction and collagen synthesis in rat hepatic stellate cells

Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present study was aimed to investigate the effects of Ang Ⅱ and angiotensin Ⅱ type 1 receptor antagonist （AT1RA） on the proliferation, contraction and collagen synthesis in HSCs.
Methods HSC-T6 rat hepatic stellate cell line was studied. The proliferation of the HSC cells was evaluated by MTT colorimetric assay while HSC DNA synthesis was measured by ^3H-thymidine incorporation. The effects of angiotensin Ⅱ and AT1RA on HSCs contraction were studied by analysis of the contraction of the collagen lattice. Cell culture media were analyzed by RT-PCR to detect secretion of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ （Col Ⅲ） and transforming growth factor β1 （TGF-β1） by enzyme linked immunosorbent assay. HSC was harvested to measure collagen Ⅰ, collagen Ⅲ and tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA expression.
Results Ang Ⅱ （（1×10^-10-1×10^-4）mol/L）stimulated DNA synthesis and proliferation in HSCs compared with untreated control cells. AT1RA inhibited angiotensin Ⅱ induced proliferation of HSCs. A linear increase in the contractive area of collagen lattice correlated with the concentration of angiotensin Ⅱ （1×10^-9-1×10^-5 mol/L） and with time over 48 hours. AT1RA blocks angiotensin Ⅱ induced contraction of collagen lattice. Col Ⅰ, Col Ⅲ and TGF-β1 levels of the Ang Ⅱ group were higher than those of control group and this increase was downregulated by AT1RA. The mRNA expressions of Col Ⅰ, Col Ⅲ and TIMP-1 were higher in HSCs from the Ang Ⅱ group than the control group and downregulated by AT1RA.
Conclusions Angiotensin Ⅱ increased DNA synthesis and proliferation of HSCs in a dose-dependent manner, stimulated the contraction of HSCs dose- and time-dependently. Angiotensin also promoted excretion of Col I, Col Ⅲ and TGF-β1 lev     

肝纤维化大鼠肝脏血管紧张素Ⅱ受体1型的表达及其与α-平滑肌肌动蛋白表达相关性研究

目的 了解血管紧张素Ⅱ受体1型(angiotensinⅡ type 1 receptor,AT1R)在肝纤维化大鼠肝脏的表达及其与胶原纤维含量和α-平滑肌肌动蛋白(α-SMA)表达的关系.方法 将30只SD大鼠随机分成正常组(n=10)和肝纤维化组(n=20).正常组正常饲养,肝纤维化组给予40% 四氯化碳(CCL4)橄榄油0.4 mL/100 g体质量背部皮下注射,每3 d注射1次,第5 w末处死两组大鼠,肝组织制备成石蜡切片后进行Masson三色染色、AT1R和α-SMA免疫组织化学染色,采集图片后用image pro plus 6.0软件对阳性表达进行累计光密度测定.对所得数据进行相关和回归分析.结果 AT1R在正常组大鼠肝脏不表达或血管周围弱表达,在肝纤维化组肝脏汇管区周围和纤维间隔周围大量表达,其主要在肝细胞浆和(或)膜表达,肝星状细胞未见表达;半定量测定及相关分析结果 显示,α-SMA与胶原纤维、AT1R与胶原纤维、AT1R与α-SMA的相关系数分别为0.958、0.971、0.990(P＜0.01).结论 AT1R在肝纤维化大鼠肝细胞大量表达,在肝星状细胞不表达,AT1R的含量与胶原纤维含量、α-SMA表达量存在正相关性.     

氯沙坦对血管紧张素Ⅱ损伤RIN-m细胞胰岛素分泌功能的保护及机制探讨

目的观察氯沙坦对血管紧张素Ⅱ(AngⅡ)损伤β细胞(RIN-m)功能的保护,并对其机制进行探讨。方法常规培养RIN-m细胞,分为空白对照组、100nmol/LAngⅡ组和氯沙坦预处理组,各组干预24h后使用放射免疫法检测基础(3.3mmol/L)和葡萄糖(16.7mmol/L)刺激下RIN-m细胞胰岛素分泌量;DCFH-DA染色流式细胞仪检测细胞内活性氧(ROS)水平;RT-PCR和Western blotting分别检测RIN-m细胞解偶联蛋白2(UCP2)mRNA和蛋白的表达。结果①各组基础胰岛分泌没有显著差异(P>0.05),在高糖刺激下,100nmol/LAngⅡ组胰岛素分泌量明显低于空白对照组(P<0.001),氯沙坦预处理组胰岛素分泌量与空白对照组无显著差异(P>0.05),但较AngⅡ组明显增加(P<0.001);②100nmol/LAngⅡ组细胞内ROS水平、UCP2mRNA和蛋白表达均较空白对照组明显增加(P<0.001),氯沙坦预处理组与空白对照组无显著差异(P>0.05),但较100nmol/LAngⅡ组显著降低(P<0.001)。结论AngⅡ损伤β细胞葡萄糖刺激胰岛素分泌(GSIS)功...     

特发性膜性肾病肾组织磷酯酶A2受体的检测及其临床意义

 目的  探讨特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者肾组织磷酯酶A₂受体(phospholipase A₂ receptor,PLA₂R)的检测情况并分析其临床意义。  方法  回顾性分析101例经临床和肾脏病理确诊为IMN并随访1年以上的患者(在本单位肾活检前均未接受激素或免疫抑制剂治疗);13例临床和病理确诊为系统性红斑狼疮Ⅴ型、乙型肝炎、干燥综合征相关等继发性膜性肾病及20例非膜性肾病患者作为对照组。检测各组患者肾组织PLA₂R及IgG分型的结果,并分析PLA₂R阳性及阴性IMN患者治疗前后尿蛋白、肾功能的变化。  结果  86.14% IMN患者肾组织PLA₂R阳性,而继发性膜性肾病患者肾组织PLA₂R阳性率仅为23.08%(vs.IMN组,P<0.001)。83.75%IMN患者肾组织PLA₂R阳性伴IgG4中度以上阳性;继发性膜性肾病患者中,无一例肾组织PLA₂R阳性同时伴IgG4中度以上阳性(vs.IMN组,P<0.01)。47例肾组织PLA₂R阳性的IMN患者予激素或激素联合免疫抑制剂治疗,随访6个月以上,85.11%患者尿蛋白缓解,而9例肾组织PLA₂R阴性的IMN患者尿蛋白缓解率只有30.0%(vs.IMN PLA₂R阳性组,P<0.01)。  结论  IMN患者肾组织PLA₂R阳性率高。肾组织PLA₂R阳性伴IgG4中度以上阳性是鉴别IMN和继发性膜性肾病的重要指标。激素或/和免疫抑制剂可以更有效地降低肾组织 PLA₂R阳性IMN患者的蛋白尿。肾组织 PLA₂R阳性可能可以作为预测激素或免疫抑制剂治疗有效与否的重要指标。     

氟伐他汀对血管紧张素Ⅱ诱导的系膜细胞AT1受体和Ⅳ型胶原表达的影响

目的:观察血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的正常大鼠肾小球系膜细胞(HBZY-1)血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 receptor,AT1R)蛋白和Ⅳ型胶原(ColⅣ)蛋白的表达情况及氟伐他汀对AT1R和ColⅣ表达的影响,探讨其肾脏保护作用的可能机制。方法:将HBZY-1细胞分为3组:①阴性对照组;②不同浓度(0.1,1.0,10μmol/L)AngⅡ刺激组;③1.0μmol/L AngⅡ加不同浓度(0.1,1.0,10μmol/L)氟伐他汀干预组,蛋白质印迹法检测各组AT1R蛋白的表达,酶联免疫吸附实验(ELISA法)检测各组ColⅣ蛋白的表达。结果:AngⅡ刺激后,HBZY-1细胞AT1R及ColⅣ的表达随AngⅡ浓度增加而增强;氟伐他汀能够剂量依赖性地抑制AT1R和ColⅣ的表达。结论:氟伐他汀能够抑制AngⅡ诱导的HBZY-1细胞AT1R和ColⅣ的表达,同时AT1R和ColⅣ的表达存在正相关,推断氟伐他汀可能通过下调AT1R影响ColⅣ的表达,进而改善高血压肾脏硬化。