阿司匹林对控制大鼠盐敏感性高血压的作用机制研究

目的探讨阿司匹林对大鼠盐敏感性高血压的调节作用及相关机制。方法 2月龄盐敏感性大鼠(Dahl SS)及其对照盐耐受性大鼠(SS-13BN)分别给予低盐(0. 12%NaCl,LS)、高盐(8%NaCl,HS)、高盐加阿司匹林灌胃((10 mg/(kg·d)),HS+ASA)饲养至8周,期间尾袖法连续测量动脉血压,8周后颈总动脉插管测量大鼠动脉血压,Real-time PCR检测肾组织炎症因子IL-6、IL-1β、TNF-α的表达,免疫荧光检测皮肤M2型巨噬细胞的数量,免疫印迹检测血管功能代表性蛋白eNOS、vWF的表达。结果 Dahl SS大鼠高盐喂养后,血压明显升高,肾组织炎症因子和血管vWF因子表达量显著增加、皮肤M2型巨噬细胞数量及血管eNOS表达量明显减少,阿司匹林能够有效改善Dahl SS大鼠高盐诱导的血压升高、炎症反应及血管功能的损伤,而SS-13BN大鼠并未出现上述情况。结论阿司匹林通过抗血小板功能抑制了Dahl SS大鼠由高盐诱导的炎症反应,抑制了血管功能损伤及高血压发生发展。     

高盐饮食对Dahl大鼠肾脏SGK1基因表达的影响

目的：通过观察高盐负荷后Dahl盐敏感大鼠肾脏血清和糖皮质激素调节蛋白激酶1（SGK1）基因的表达,探索其在盐敏感性高血压形成中的作用。方法对Dahl盐敏感大鼠和对照组SS-13BN大鼠分别给予正常盐[0.3%氯化钠（NaCl）]和高盐（8%NaCl）饮食3周干预,测定血压,采用Real-time PCR检测肾脏SGK1基因信使核糖核酸（mRNA）。结果 SS高盐饮食组大鼠及SS-13BN高盐组大鼠血压均比其低盐饮食组高;与13BN组相比,SS高盐组血压较低盐组升高幅度更为显著;Dahl盐敏感大鼠高盐组肾脏SGK1的表达较低盐组显著增加,同时也显著高于高盐组SS-13BN大鼠。结论高盐引起Dahl盐敏感大鼠肾脏SGK1的表达异常增加可能是盐敏感性高血压形成的重要原因。     

高盐负荷上调SHR胸主动脉、肠系膜上动脉壁AT1和AT2受体表达实验研究

目的:以自发性高血压大鼠(SHR)为研究对象,探讨动脉血管壁胶原成分、血管紧张素Ⅱ受体(ATR)AT1和AT2亚型蛋白表达的增龄性改变及高盐负荷对它们的影响。方法:雄性SHR60只,随机分为低盐组(0.4%NaCl,n=30)和高盐饮食组(4%NaCl,n=30)干预3周,测量血压后;胸主动脉及肠系膜上动脉石蜡切片Mallory染色法观察壁纤维化程度,免疫组化SABC法测定ATR蛋白表达。结果:高盐负荷后SHR大鼠的血压呈现明显升高(P<0.05);胸主动脉和肠系膜上动脉壁Ⅰ型和Ⅲ型胶原纤维沉积亦随增龄增多,高盐负荷会加重这一趋势(P<0.05);高盐负荷均能显著增加动脉壁AT1和AT2表达(P<0.01),而以肠系膜上动脉壁改变较为显著,但是对AT1/AT2比值无影响(P>0.05)。结论:高盐负荷可导致SHR大鼠血管壁重塑,血管壁局部ATR的改变可能是SHR大鼠血管壁重塑的机制之一,减少盐的摄入对预防高血压动脉病变的发生和发展有着重要的意义。     

川芎嗪及丹参对正常及高血压大鼠动脉平滑肌Ca~(2+)内流的动力学影响

钙(Ca)与高血压发病密切相关.血管平滑肌(VSM)细胞内持续的高钙水平,导致VSM紧张,最终引起高血压.胞内高钙浓度的主要原因是Ca~+内流与外流机制障碍。正常时,Ca~(2+)内流与外流速率处于动态平衡,维持着细胞内低外高的钙的浓度差。本工作比较了正常及高血压大鼠主动脉(AS)及肠系膜动脉(MS)平滑肌Ca~(2+)内流情况,并观察川芎嗪及丹参对Ca~(2+)内流的影响。     

内皮─氧化氮的减少引起Dahl高血压大鼠异常的血管反应

本文研究目的在于观察Dahl高血压大鼠对去甲肾上腺素（NE）收缩反应增强，对乙酰胆碱（ACH）舒张反应减弱，是否与血管内皮NitricOxide（NO）有关。7—8周龄雄性Dahl盐敏感（DS）大鼠和盐抵抗（DR）大鼠，各随机分两组，分别给予正常盐或高盐饮食，每周尾套管法测血压和体重，4周后麻醉状态下取胸主动脉，用于离体血管反应性研究。结果显示：高盐饮食的DS大鼠尾动脉血压明显升高，NE诱导的收缩反应也明显高于其它三组，去内皮及体外L—NAME的处理，可以消除这一差别。同时Dahl高血压大鼠，ACh诱导的舒张反应也明显减弱。体外Larginine的使用，不同程度地降低了NE诱导的收缩反应，但不能废除组间差异。结论：NO合成酶功能障碍可能是Dahl高血压大鼠异常血管反应的原因。     

抗高血压因子对正常及高血压动物动脉平滑肌Ca~(2+)内流的影响

通过实验观察到从自发性高血压大鼠(SHR)红细胞提取的抗高血压因子(AHF)可以明显抑制SHR血管平滑肌(VSM)Ca~(2+)内流,呈剂量依赖关系。而对正常血压大鼠(WKY)无影响。这种抑制作用及与剂量的关系在肠系膜动脉比主动脉更明显。结果表明,AHF的降压作用可能与抑制VSM Ca~(2+)内流有关。     

Wistar大鼠形成盐敏感高血压后动脉组织端粒酶的活性变化

目的 :探讨wistar大鼠形成盐敏感高血压前后动脉组织端粒酶的活性变化。方法 :采用鼠尾测血压计测量血压。选择 1 2只形成感觉神经变性盐敏感高血压wistar大鼠及 1 0只对照同龄wistar大鼠 ,麻醉下取外周动脉组织 ,用PCR ELISA方法测定高血压及对照大鼠动脉组织端粒酶活性。结果 :正常血压大鼠动脉组织 1 0 %端粒酶阳性 ,而高血压大鼠 5 0 %阳性 ,差异显著 (P <0 .0 5 ) ,两组动脉组织端粒酶活性A值比较亦具有差异性显著 (P <0 0 5 )。结论 :大鼠形成高血压后动脉组织端粒酶再次激活 ,而端粒酶作为细胞增殖的分子水平标志 ,提示盐敏感性高血压形成后 ,存在血管壁增殖 ,即高血压与血管壁增殖或血管重构互为因果     

血小板活力与胞外钙离子浓度的关系

作者对血小板活力与胞外Ca~(2+)浓度间的关系作了观察。证明在家兔和大鼠的柠檬酸盐抗凝的富含血小板血浆中,以不同的激活剂激活血小板时,其变形速率不因外加不同剂量的Ca~(2+)有所改变;而释放和聚集活力则随外加Ca~(2+)的剂量增加而增加。因此在动物试验中,在其富含血小板血浆中,外加一定量的Ca~(2+)以使血小板活力充分发挥很有必要,以满足当时血小板赖钙反应的进行。     

高血压心力衰竭大鼠动物模型的研制

目的 研制高血压引起的心衰大鼠动物模型.方法 将18只Dahl盐敏感性大鼠分为正常组和模型组并分别使用0.3%NaCl低盐饲料和8%NaCl高盐饲料喂养大鼠20周,观察大鼠行为及体征,检测大鼠血压、 血清氨基末端脑钠肽前体(N-terminal Pro-brain natriuretic peptide,NT-proBNP)含量,彩色超声多普勒检测大鼠左室射血分数(left ventricular ejec-tion fraction,LVEF)和左室短轴缩短率(left ventricular fractional shortening,LVFS)及电镜观察HE染色心肌细胞以及肾脏组织等.结果 正常组大鼠血压一直维持在140 mmHg左右,而模型组大鼠从进食高盐饲料后血压保持持续上升,最高可达250 mmHg;与正常组比较,模型组的NT-proBNP、LVEF、LVFS在统计学上有显著差异(P<0.01).结论 本研究制作的动物模型可较好地模拟正常大鼠继发高血压病进而发展成高血压心衰大鼠模型的过程,可用于高血压心力衰竭疾病的研究.     

围产期高盐饮食程控雄性子代大鼠动脉血压盐敏感性

目的探讨围产期高盐饮食对子代Sprague-Dawley大鼠动脉血压及盐敏感性程控作用的性别差异及其可能机制。方法围产期给予高盐饮食(8%NaCl)和正常饮食(1%NaCl),监测雄性及雌性子代体重发育,并采用无创性尾套法测量血压及心率变化;后给予各组子代高盐饮食14 d观察其盐敏感性,并于测量结束后以放射免疫学方法检测血清及脑组织肾素-血管紧张素-醛固酮系统各成分及应激相关激素水平。结果围产期高盐饮食对子代大鼠青春期动脉血压无显著影响,但显著提高雄性子代的盐敏感性,且雄性子代血清血管紧张素II升高,而肾上腺皮质激素释放激素和皮质醇低于正常组,雌性子代则未观察到相同效应。结论围产期高盐饮食对子代动脉血压盐敏感性具有程控作用,并具有显著的性别差异,其机制可能与子代肾素-血管紧张素-醛固酮系统功能异常及应激反应性变化有关。     

不同浓度钠盐饮食对自发性高血压大鼠血压及左心室肥厚的影响

目的观察不同浓度钠盐饮食对自发性高血压大鼠(SHR)血压及左心室肥厚的影响,并探讨其可能机制。方法SHR大鼠30只分为3组:1高盐饮食组SHRh(n=10),饮用含4%Na Cl盐水;2正常盐饮食组SHRn(n=10),饮用0.9%Na Cl盐水;3低盐饮食组SHRl(n=10),饮用含0.4%Na Cl盐水。以Wistar大鼠作为对照组(n=10),正常盐饮食,饮用0.9%Na Cl盐水。适应性喂养1周,实验喂养12周。测定大鼠血压动态变化及左心室重量指数(LVI)。结果 SHR大鼠与Wistar大鼠比较血压明显升高,左心室重量指数升高;高钠饮食及低钠饮食组较正常饮食组后期血压更高,左心室重量指数也相应升高。结论钠盐对SHR大鼠高血压及左心室肥厚的影响存在"J曲线"现象。     

高盐对SD大鼠肾脏骨调素mRNA表达的影响

OBJECTIVE: To investigate the effect of high-salt diet on the expression of osteopontin (OPN) mRNA and its protein in Sprague-Dawley rat kidney. METHODS: Forty-eight male SD rats aged 10 weeks receiving normal salt diet were enrolled in study, and were divided into two groups and fed with high salt diet (4%NaCl) or normal salt diet (0.6%NaCl) for 12 weeks respectively, with 24 rats in each group. Tail systolic blood pressure and bodyweight were measured in all rats every week. At the end of 4th, 8th and 12th week, 6 rats in each group were sacrificed for detection of the expression of OPN mRNA and its protein in the kidney with quantitatine real-time (QRT)-PCR and immunohistochemistry, respectively. RESULTS: No significant difference was found in blood pressure, bodyweight and kidney weight/bodyweight between high-salt diet group and normal salt diet group (P>0.05). The expression of OPN mRNA (0.27+/-0.16 vs 0.15+/-0.13, P<0.05) and its protein (0.78+/-0.15 vs 0.61+/-0.11, P<0.01) in SD rat kidney with high-salt diet were up-regulated at the end of 12th week compared with the rats with normal salt diet. CONCLUSIONS: High-salt diet increase the expression of OPN mRNA and its protein in SD rat kidney. Renal injury induced by high salt intake might be independent of blood pressure change.     

盐摄入量对腹膜透析大鼠残余肾功能的影响

Objective To assess the effect of salt intake on residual renal function in rats and explore the possible mechanism. Methods SD rats were 5/6-nephrectomized to induce chronic renal failure followed by peritoneal dialysis for 4 weeks (n=18) or without dialysis treatment (control group; n=18). In both groups, the rats were divided into 3 subgroups and were given low-salt diet (0.02% NaCl), normal salt diet (0.4% NaCl), and high-salt diet (4% NaCl). After 8 and 12weeks, blood pressure and creatinine and sodium levels in the blood, urine, and peritoneal dialysate of the rats were examined. Glomerular sclerosis, tubulointerstitial fibrosis, and protein expression levels of RAS components (ACE-1, AGT, and AT-1) in renal cortical tissue of the rats were evaluated. Results The residual renal function of the rats all decreased especially in rats with high salt intake for 8 and 12 weeks. In peritoneal dialysis group, the rats with high-salt diet showed signficiantly increased renal interstitial fibrosis score (P=0.036), glomerular sclerosis index (P=0.045), systolic blood pressure (P=0.004), diastolic blood pressure (P=0.048), and renal expressions of AGT, ACE-1, and AT1 (P<0.05) as compared with those with normal salt intake. In the rats fed the same high-salt diet, the renal interstitial fibrosis score, glomerular sclerosis index, diastolic blood pressure increase, and renal AGT and ACE-1 expression levels were significantly lower in the peritoneal dialysis group than in the control group (P<0.05). A positive correlation was noted between the reduction of residual renal function and sodium intake in the rats. Conclusion In rats with chronic renal failure, high salt intake promotes the activation of the renal RAS system, increases blood pressure, and agrevates renal fibrosis to accelerate the decline of residual renal function, and peritoneal dialysis partially reduces the damage of residual renal function induced by high-salt diets by removing excessive sodium.     

不同钙、镁比例饮用水对相对高草酸尿症大鼠肾结石形成及代谢的影响

[摘要] 目的 探讨低于硬水标准的不同钙、镁比例饮用水对相对高草酸尿症大鼠肾结石形成及代谢的影响。 方法 将42只SPF级雄性Sprague-Dawley大鼠随机分成7组（n=6）：空白组、模型组、高钙低镁组、中钙低镁组、低钙低镁组、低钙中镁组和低钙高镁组,空白组饮用纯净水,模型组饮用0.1%乙二醇（EG）配制水,高钙低镁组、中钙低镁组、低钙低镁组、低钙中镁组、低钙高镁组各干预组在模型组基础上给予不同钙、镁浓度比例的饮用水,浓度比例分别为360/10、120/10、10/10、10/40、10/80（mg/L）。各组大鼠在相同环境下饲养8周后,收尿液、血液及双肾标本,左肾做H&E染色石蜡切片,光学显微镜观察草酸钙结晶情况;分别测定大鼠24h尿量、尿钙、尿镁、尿草酸、尿枸橼酸排泄量及血钙、血镁、血肌酐以及血尿素氮浓度。 结果 大鼠肾重量低钙低镁组、低钙中镁组均较空白组比较显著增加（P<0.05）。低钙中镁组血尿素氮浓度较空白组、模型组比较均显著升高（P<0.05）。各组大鼠体重变化、摄水量、24h尿量、血钙、血镁和血肌酐等的比较无统计学差异（P>0.05）。24h尿镁排泄量低钙中镁组较空白组显著增加（P<0.05）。24h尿草酸排泄量模型组、低钙低镁组、低钙中镁组均显著高于空白组（P<0.01）,中钙低镁组也较空白组显著升高（P<0.05）;除低钙低镁组外,其余干预组24h尿草酸排泄量均显著低于模型组（P<0.01）。尿钙、24h尿枸橼酸排泄各组均无显著性差异。血钙、血镁、血肌酐各组间均无显著性差异。各组尿结晶均为阴性。各组肾组织病理学检查各组均未见结晶形成,肾小球、小管细胞大小正常,排列整齐、规则,肾小管管腔无扩张,管腔内无坏死脱落样物质。结论 相对高草酸尿症造模对大鼠体内钙和镁的代谢、尿结晶及成石没有影响;在饮用水硬度低于硬水标准下,随钙镁总量（硬度）升高24h尿草酸排泄量减低;单纯高草酸尿症成石草酸浓度或量需要达到一定水平才能显示成石作用;而尿枸橼酸作为结石的保护性因素,它是相对独立的,不受造模及不同钙、镁比例饮用水影响。     

Effect of SJAMP on human platelet cytoplasmic Ca2+

Summary Using the method of dual-wavelength measurement of platelet [Ca²⁺]_i and Fura-2 as the Ca²⁺ fluorophore probe, we measured the effect of acidic Mucopolysaccharide fromSticopus Japonicus Selenka (SJAMP) on platelet [Ca²⁺]_i. The results showed that the most significant increase in platelets [Ca²⁺]_i was seen when the concentration of SJAMP was 100μg/ml and the elevation of normal platelet [Ca²⁺]_i was 93.96 ± 10.24 nmol/L (n=10). In the presence of extracellular Ca²⁺ (1 mmol/L), the magnitude of platelet [Ca²⁺]_i response to SJAMP was increased and the [Ca²⁺]_i could reach 116.72±10. 66 nmol/L (n = 10). On the other hand, the magnitude of increased platelet [Ca²⁺]_i induced by SJAMP was smaller and the duration of [Ca²⁺]_i reaching the highest level was longer when compared with other platelet aggregation agents. In the mean time, if platelets were first incubated with cyclooxygenase inhibitor, the rise of [Ca²⁺]_i evoked by SJAMP was inhibited. The results indicated that the mechanism of the rise of [Ca²⁺]_i induced by SJAMP might be dependent upon the generation of prostaglandin endoperoxides and(or) TXA₂. This project was supported by grant from the National Nature Science Foundation of China (No. 39370322).     

胡颓子叶对豚鼠离体气管平滑肌收缩功能的影响

目的 研究胡颓子叶乙醇提取物正丁醇部位（胡颓子叶正丁醇部位）对正常及多种致痉剂诱导的豚鼠气管平滑肌收缩功能的影响。方法 制备豚鼠离体气管平滑肌螺旋条,在其正常状态下以及用乙酰胆碱、组胺、氯化钾、无钙下乙酰胆碱诱导细胞内钙释放和高钙下诱发细胞外钙内流条件下,观察胡颓子叶正丁醇部位对离体气管张力的影响。结果 胡颓子叶正丁醇部位对静息状态下的豚鼠离体气管平滑肌有明显的舒张作用,使乙酰胆碱和组胺的量效曲线发生明显右移,抑制加入高钾或高钙后引发细胞外钙内流导致的收缩。结论 胡颓子叶正丁醇部位能明显抑制正常状态及多种致痉剂诱发的豚鼠气管平滑肌收缩。     

Effects of captopril on platelet cytosolic free Ca2+ concentrations and on suppression of cell proliferation in culture

Summary In order to investigate the feasibility of angiotensin converting enzyme inhibitors (ACEIs) in preventing the development of atherosclerosis and restenosis after coronary angioplasty and to study their mechanisms, we measured the platelet cytosilic free Ca²⁺ concentration ([Ca²⁺]i) and observed the effects of captopsil on platelet [Ca²⁺]i in rabbits and also observed the inhibitive action on fibroblast proliferation in culture. The results showed that resting platelet [Ca²⁺]i, ADPor thrombin-stimulated platelet elevation amplitude after administration of captopril (12.5 mg, twice daily) for 15 days were significantly reduced in comparison with those before administration. And captopril also significantly inhibited fibroblast proliferation or reduced³H-thymidine (³H-TdR) incorporation in culture in a dose-depdendent manner. These findings suggest that ACEIs are promising drugs to reduce restenosis incidence after coronary angioplasty and to prevent atherosclerosis as well as provide a new explanation for their effects of suppressing cell proliferation.