全反式维甲酸对高血压大鼠体内apelin-APJ信号系统的影响

目的:探讨全反式维甲酸(atRA)对高血压大鼠体内心血管活性多肽apelin及其受体APJ信号的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射atRA,为期1月。分别用实时荧光定量多聚酶链式反应(PCR)与免疫印迹技术测定atRA治疗后SHR体内apelin和APJ受体的表达情况。结果:与WKY对照组相比,SHR心脏组织中apelin及其受体APJ的 mRNA和蛋白表达明显下调(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中apelin、APJ表达出现上调(P均<0.05)。结论:长期atRA治疗促进SHR大鼠心脏组织中apelin及其受体APJ的表达增加,提示转录调节剂atRA很可能对人类高血压病防治具有积极作用。     

全反式维甲酸对肺气肿大鼠氧化应激的影响

目的观察全反式维甲酸（ATRA）对猪胰蛋白酶（PPE）致大鼠肺气肿模型的氧化应激的影响。方法选60只Wistar大鼠随机分为对照组（N）和模型组（E）,棉籽油组（C）,小剂量ATRA治疗组（L）,中剂量ATRA治疗组（M）,大剂量AT-RA治疗组（H）各10只为研究对象,用大、中、小剂量ATRA和棉籽油注入大鼠腹腔内进行治疗。30天后处死解剖大鼠,测量大鼠肺体积,肺泡形态学,肺组织SOD活力和MDA含量。结果 E、C、L、M、H组大鼠肺体积,肺泡形态学,氧化应激水平均明显大于N组（P〈0.05）;L组肺组织SOD活力较E组显著增高;L、M组肺组织MDA含量较E组显著降低（P〈0.05）。结论肺气肿模型大鼠用低剂量ATRA治疗对肺泡有较好修复作用,可提高肺组织SOD活力,降低肺组织MDA含量,可以起到抗氧化保护肺组织作用。     

全反式维甲酸对高血压大鼠体内ACE2表达与一氧化氮信号的影响

目的:探讨全反式维甲酸(atRA)对高血压大鼠体内血管紧张素转换酶2(ACE 2)基因表达及一氧化氮(NO)信号的影响。方法:采用自发性高血压大鼠(SHR)及其同源对照W KY大鼠,经腹腔注射atRA,为期1月。分别用实时荧光定量PCR,N orthern印迹及免疫印迹技术测定atRA治疗后SHR体内ACE 2、血管紧张素Ⅱ1型受体(AT1)的表达情况,以硝酸还原酶法检测血清NO水平。结果:与W KY对照组相比,SHR心脏ACE 2的mRNA和蛋白表达下调[mRNA拷贝数比值:(0.06±0.02)vs.1;蛋白吸光度比值:(0.73±0.05)vs.1,P均<0.01],atRA(低、高剂量atRA组)治疗后SHR心脏ACE 2表达上调[mRNA:(0.23±0.08),(0.53±0.18)vs.(0.06±0.02);蛋白水平上升:(0.9±0.07),(0.92±0.08)vs.(0.73±0.05),P均<0.05],同时出现AT1表达降低、血清NO水平增高以及血压下降(P均<0.05)。结论:长期atRA治疗促进SHR大鼠心脏ACE 2的表达增加,导致体内NO增加,血压下降,提示转录调节剂atRA很可能对人类高血压病防治具有一定的价值。     

氧化应激与高血压

氧化应激（oxidative stress）：是指机体遭受各种有害刺激时,机体或细胞内自由基的产生和抗氧化防御之间严重失衡,活性氧在机体或细胞内蓄积引起细胞毒性反应,从而导致组织损伤过程。     

全反式维甲酸对大鼠肾脏表面活性蛋白D表达的影响

目的探讨全反式维甲酸（atRA）对肾盂肾炎大鼠肾脏表面活性蛋白D（SP-D）表达的影响,以及肾脏炎症程度与SP-D表达之间的关系。方法将24只SPF级雌性Wistar大鼠随机分为4组：正常对照组、假手术组、肾盂肾炎模型组、肾盂肾炎＋atRA治疗组。采用致肾盂肾炎大肠杆菌肾筋膜下注射法制造肾盂肾炎模型。HE染色法观察肾组织病理改变,免疫组化法观察SP-D表达部位及强度。结果与对照组相比,模型组炎症评分和SP-D表达强度均显著增加,治疗组炎症评分和SP-D表达强度也显著增加,但低于模型组（P均〈0.05）,假手术组与对照组相比无统计学差异（P〉0.05）。肾脏炎症程度与SP-D表达强度呈正相关（r=0.842,P〈0.05）。结论SP-D可能在肾脏的先天免疫与炎症反应中有重要调节作用;atRA可能通过下调SP-D表达,减轻肾脏炎症损伤程度。     

全反式维甲酸对培养的大鼠动脉平滑肌细胞增殖的影响

目的 研究全反式维甲酸(ATRA)对培养的大鼠动脉平滑肌细胞(VSMCs)的影响。方法 血管平滑肌细胞采用组织贴块法培养。ATRA(2.5×10-6mol/L)分别作用于经PDGF—BB(10 ng/ml)和20％FCS刺激后的VSM—Cs,作用24h后分别行3H—TdR,3H—Leucine掺入实验测定。结果 ATRA明显抑制由PDGF—BB(10ng/ml)和20％FCS促进的VSMCs的DNA和蛋白质合成。结论ATRA具有抑制VSMCs增殖的作用。     

全反式维甲酸对培养大鼠主动脉平滑肌细胞Cyclin A表达水平及增生的影响

目的探讨全反式维甲酸(ATRA)对培养的大鼠主动脉平滑肌细胞细胞周期蛋白A(Cyclin A)表达水平及增生的影响.方法血管平滑肌细胞采用组织贴块法培养.ATRA(2.5×10-6mol/L)作用于经20%FBS刺激后的VSMC,作用24h后分别行蛋白印迹检测Cyclin A蛋白表达和3H-TdR掺入实验测定. 结果ATRA明显抑制由20%FBS促进的DNA合成[每孔每分钟脉冲数(3725.48±643.77)对(11567.09±1974.67)],同时降低Cyclin A蛋白的表达[平均光密度(122.50±9.59)对(135.92±11.95)]. 结论ATRA抑制Cyclin A蛋白的表达是抑制VSMC增生的原因之一.ATRA可能成为预防和治疗动脉粥样硬化(AS)的有效药物.     

全反式维甲酸、马洛替酯对大鼠肝纤维化的治疗作用

目的 观察全反式维甲酸、马洛替酯对小剂量ＣＣｌ４诱导的肝纤维化大鼠治疗作用。方法 对肝脏Ⅰ、Ⅲ、Ⅳ、Ⅴ型胶原及结蛋白进行 化染色和计算机图像分析,并用电镜观察肝细胞、Ｉｔｏ细胞超微结构的变化,结果 ＣＣｌ４诱导的大鼠肝纤维化可有一定程度的自然恢复。全反式维甲酸能抑制Ｉｔｏ细胞的激活与增殖、马洛替酯有减轻炎症瓜的作用,但效果较秋水仙碱差。结论 全反式维甲酸、马洛替酯有轻微的治疗肝纤维化的作用。     

三氧化二砷和全反式维甲酸治疗急性早幼粒细胞白血病疗效的对 …

目的 用三氧化二砷（Ａｓ２Ｏ３）及全反式维甲酸（ＲＡ）治疗急性早幼粒细胞白血病（ＡＰＬ）７５例,进行临床疗效的对比分析。方法 随机分ＡＰＬ患者３７例及３８例两组,临床观察三氧化二砷,全反式维甲酸对ＡＰＬ的缓解率,无病生存期及其毒副作用。结果Ａｓ２Ｏ３组、ＲＡ组的完全缓解（ＣＲ）率分别为８６．４％及８４．２％（Ｐ〉０．０５）;两组缓解期及无病生存期亦无明显差异,且Ａｓ２Ｏ３治疗剂量的毒副作用小,均可     

全反式维甲酸对糖尿病肾病肾小球p-cadherin表达的影响

目的 观察全反式维甲酸(ATRA)对糖尿病肾病(DN)肾小球p-cadherin表达的影响,明确其对肾脏的保护作用.方法 应用链脲佐菌素(STZ)建立DN大鼠模型.ATRA治疗组(n=10)给予ATRA每天20 mg/kg灌胃,对照组(C组,n=10)、DN组(n=10)以等量蒸馏水灌胃.采用ELISA法检测大鼠24 h尿液中白蛋白及肌酐值;免疫组织化学和胶体金免疫电镜法观察p-cadherin蛋白表达的部位及数量;RT-PCR法检测p-cadherin mRNA表达. 结果 ATRA组肾重及尿白蛋白/尿肌酐比值较DN组明显下降(P＜0.01).免疫组化检测结果示ATRA组p-cadherin蛋白表达较DN组上调,与C组相比无明显下降.电镜结果示DN组免疫金染色的p-cadherin蛋白较C组减少.RT-PCR结果示ATRA组p-cadherin mRNA表达较DN组上调,与C组无明显差异.结论 ATRA可逆转DN大鼠早期DN肾小球足细胞p-cadherin蛋白的下调,由此降低早期DN尿白蛋白排泄量,延缓DN进展.     

Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats

OBJECTIVE: Studies show general agreement that all-trans retinoic acid (atRA) has been linked to the regulation of G protein-coupled receptor (GPCRs) signaling. To further validate effects of atRA on the cardiovascular GPCRs, the present study was designed to assess whether atRA will modulate orphan receptor APJ, a homologue of angiotensin II type 1 (AT(1)) receptor. METHODS: Real-time polymerase chain reaction and Western blot methods were performed to examine the expression of APJ and its endogenous ligand apelin in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats after chronic atRA treatment. RESULTS: APJ and apelin expression were markedly depressed in placebo-treated SHR, compared with WKY rats (p<0.01). However, in atRA-treated SHR, a significant upregulation of APJ and apelin expression was observed in both heart and aorta (p<0.05), accompanied by a reduction of AT(1) expression, an elevation of serum nitric oxide levels and a subsequent decrease of blood pressure. CONCLUSIONS: Chronic atRA treatment activates gene and protein expression of APJ and apelin and reduces blood pressure in SHR, suggesting that atRA may regulate the balance between apelin-APJ and angiotensin II-AT(1) signaling and have potential clinical value in the prevention and treatment of human hypertension.     

Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats

There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.     

α-硫辛酸降低糖尿病大鼠肾脏氧化应激水平

将大鼠分成正常对照（NC）组、糖尿病（DM）组及糖尿病加α-硫辛酸（DM＋ALA）组进行实验。4周后DM组24小时尿白蛋白（UAlb/24h）、肾重/体重（KW/BW）和丙二醛（MDA）含量均较NC组增加，总超氧化物歧化酶（TSOD）活性降低，谷胱甘肽过氧化物酶（GSH-Px）活性升高，过氧化氢酶（CAT）活性无变化；DM＋ALA组较DM组UAlb/24h、KW/BW和MDA水平降低，TSOD、GSH-Px和CAT活性无改变。结果说明，ALA能减低DM大鼠肾皮质氧化应激水平，延缓糖尿病肾病进展。     

肾衰竭患者静脉铁剂诱导的氧化应激状态及硫辛酸干预作用的研究

目的 观察慢性肾衰竭患者由静脉铁剂诱导的氧化应激,探讨硫辛酸对其的预防作用.方法 慢性肾衰竭非透析患者20例,每位患者均先后接受单纯静脉铁剂治疗(Fe组)及硫辛酸预防性处理(LA Fe组).测定并分析静脉铁剂滴注前(0小时)和滴注后1小时、2小时及3小时血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)、丙二醛(MDA)水平的变化.结果 Fe组血清SOD、GSH-px水平下降,在1小时时达谷值(P<0.01,P<0.05),血清MDA水平明显升高,在1小时时达峰值(P<0.01).LA Fe组血清SOD、GSH-px及MDA水平变化趋势与Fe组相似,但与Fe组比较,血清SOD、GSH-px水平在各时间点均有显著性升高(P<0.01),MDA水平在各时间点均显著下降(P<0.01).结论 慢性肾衰竭患者接受静脉铁剂治疗时,可以诱导氧化应激反应在短期内急性加剧.静脉铁剂应用前静脉滴注硫辛酸可在一定程度上减轻这种氧化应激状态.     

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm²/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm²/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge.     

仙珍骨宝对维甲酸致大鼠骨质疏松的影响

目的 探讨仙珍骨宝对维甲酸致大鼠骨质疏松的影响.方法 4月龄未交配的SPF级雌性SD大鼠24只,随机分成正常对照组、维甲酸组、仙珍骨宝组,持续给药28 d.大鼠处死后取股骨进行骨密度的测量,取第4腰椎进行生物力学参数测量,取胫骨上段测定骨形态计量学参数.结果 仙珍骨宝组腰椎生物力学指标均高于维甲酸模型组(P<0.05),但股骨骨密度和胫骨上段骨形态计量学参数与维甲酸模型组无明显差别(P>0.05).结论 仙珍骨宝可对抗维甲酸致大鼠腰椎生物力学性能的降低,但对骨密度和骨形态计量学参数无明显影响.     

应激大鼠胃黏膜氧化应激指标受褪黑素影响的研究

目的探讨褪黑素干预应激大鼠胃黏膜氧化应激指标影响的研究.方法采用浸水-束缚(WIR)应激实验复制大鼠应激性溃疡模型.应激前30 min,MT(melatonin)5、20mg·kg-1和应激组大鼠分别腹腔注射MT 5、20mg·kg-1和等体积生理盐水.应激6h后,观察各组大鼠胃黏膜病变情况,对溃疡指数(UI)进行评分,同时检测各组大鼠胃黏膜内丙二醛(MDA)含量、胃黏膜超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)水平.结果WIR应激6h后,应激组大鼠胃黏膜MDA水平显著高于对照组(P＜0.01).MT 5、20mg·kg-1组较应激组MDA水平显著下降(P＜0.01),且MT 20mg·kg-1组显著低于MT 5mg·kg-1组(P＜0.01).应激组大鼠SOD、GSH活性较对照组明显降低(P＜0.01),MT 5、20mg·kg-1组较应激组SOD、GSH活性有升高趋势.比较各组UI发现,MT 5、20mg·kg-1组UI显著低于应激组(P＜0.01),其中MT 20mg·kg-1组UI显著低于MT 5mg·kg-1组(P＜0.05).结论褪黑素通过其抗氧化的作用对应激大鼠胃黏膜损伤起保护作用.     

1型糖尿病患者血浆视黄酸浓度的变化

1型糖尿病(T1DM)患者26例,2型糖尿病(T2DM)患者33例,健康对照者30例,HPLC法检测各组血浆全反式视黄酸(ATRA)浓度。与T2DM组及健康组比较,T1DM组血浆AT-RA浓度升高(9.2±2.8μg/L比5.8±1.6μg/L;9.2±2.8μg/L比6.1±1.7μg/L),后两者差异无统计学意义。