福辛普利对高脂诱发动脉粥样硬化血管内皮细胞黏附分子-1 mRNA表达的影响

目的利用高脂诱发的动脉粥样硬化模型观察了血管紧张素转换酶抑制剂福辛普利(fosinopril)的抗动脉粥样硬化作用.方法将建立动脉粥样硬化模型日本大耳白兔32只,随机分为三组对照组8只;高胆固醇组11只;福辛普利组13只.检测如下指标⑴计算主动脉粥样斑块面积.⑵测定血浆脂蛋白水平及低密度脂蛋白(LDL)氧化易感性.⑶RT-PCR检测组织中血管内皮细胞黏附分子(VCAM-1) mRNA表达的水平.结果福辛普利组和高脂组与对照组相比总胆固醇和甘油三酯水平明显升高,但二组间差异无显著性(P>0.05).福辛普利组动脉粥样斑块面积明显低于高胆固醇组[(26±5.4)% 比 (41±9.6)%,P<0.05]; 与高脂组比较福辛普利明显延长CuSO4诱导的LDL脂蛋白氧化反应的潜伏期(150 min 与240 min,P<0.001).福辛普利组主动脉VCAM-1/GAPDH mRNA比值低于高胆固醇组(0.90±0.35和1.40±0.51,P<0.05).福辛普利组明显降低了主动脉组织中VCAM-1的mRNA的表达.结论血管紧张素转换酶抑制剂福辛普利通过抑制低密度脂蛋白的氧化及黏附分子VCAM-1的表达延缓早期的动脉粥样硬化病变.     

咪达普利与福辛普利对糖尿病大鼠心肌超微结构的影响

目的 用咪达普利(达爽)及福辛普利(蒙诺)两种血管紧张素转换酶抑制剂(ACEI)对实验性糖尿病大鼠进行早期干预,观察两药在改善糖尿病大鼠心肌超微结构方面的作用.方法 用链脲佐菌素对30只SD大鼠进行腹腔注射,建立实验性糖尿病大鼠模型.将建模成功的动物随机分为糖尿病组(9只),咪达普利干预组(9只),福辛普利干预组(10只),另外取10只SD大鼠作为正常对照组.10 w后,观察各组大鼠心肌的超微结构.结果 糖尿病组大鼠的心肌肌原纤维走行紊乱,肌节破坏断裂,长短不一,肌丝灶性溶解、消失;闰盘排列有断裂现象,线粒体肿胀变形、嵴稀疏、排列紊乱,结构不清.心肌内微血管基底膜增厚,间质胶原纤维增生.咪达普利治疗组与福辛普利治疗组心肌超微结构均有所改善,福辛普利效果更佳.结论 咪达普利和福辛普利均可延缓实验性糖尿病大鼠心肌超微结构的病理性改变,后者优于前者.     

福辛普利对糖尿病肾病小鼠基因表达的影响

目的应用基因芯片技术研究福辛普利对糖尿病肾病（DN）小鼠肾脏基因表达谱的影响。方法分别检测福辛普利治疗组、未经治疗DN组、正常组小鼠肾脏基因的差异表达变化,筛选出差异表达基因,用生物信息学对检测结果进行分析,应用半定量RT-PCR验证差异表达基因。结果两张芯片相比,福辛普利治疗后糖尿病小鼠肾脏发生显著性差异表达变化的基因共有60个。差异表达基因主要涉及物质代谢、炎症与免疫反应、转录等。结论福辛普利可通过多种途径在基因水平上起到对DN的保护作用。     

凋亡基因在心肌梗死的表达及血管紧张素转化酶抑制剂的干预作用

目的探讨凋亡基因对大鼠心肌梗死的表达及血管紧张素转化酶抑制剂(ACEI)的干预作用。方法将大鼠随机分为假手术组、梗死模型组、梗死模型 福辛普利小剂量组、梗死模型 福辛普利大剂量组,用逆转录-聚合酶链反应(RT-PCR)方法检测大鼠心肌梗死24h和4周时心肌细胞内凋亡抑制基因Bcl-2与凋亡基因Bax、P53、Fas的mRNA表达量,并探讨它们之间的相互关系。结果急性心肌梗死24hBcl-2表达下降,福辛普利促进其高表达,Bax、P53、Fas增高,福辛普利抑制其表达;急性心肌梗死4周,Bcl-2表达下降,福辛普利促进其表达,Bax、P53表达变化不大,福辛普利对其表达无影响,Fas高表达,福辛普利抑制其表达。结论大鼠急性心肌梗死后心肌细胞存在凋亡现象,Bcl-2表达下降,Bax、P53、Fas表达上调介导心肌梗死后心肌细胞凋亡的发生。ACEI可通过干预上述基因抑制急性心肌梗死后的心肌细胞凋亡。     

福辛普利联合吲哒帕胺治疗老年高血压疗效观察

目的 观察福辛普利并吲哒帕胺联合治疗老年高血压的疗效与不良反应.方法 入选老年原发性高血压病98例,随机分成治疗组49例和对照组49例.比较福辛普利和吲哒帕胺联合治疗与单用福辛普利治疗老年高血压的疗'效及不良反应.结果 福辛普利和吲哒帕胺联合治疗高血压有效率达94.5%,明显高于单用福辛普利组73%.结论 福辛普利与吲哒帕胺联合治疗高血压有协同作用,且能减少不良反应.     

福辛普利防治心肌肥厚和钙超载的实验研究

目的　研究福辛普利对鼠实验性高血压心肌肥厚及钙超载的影响。方法　以腹主动脉部分狭窄大鼠为模型 ,观察福辛普利对血压、心肌重量及超微结构、钙含量、肌浆网钙泵功能的影响。结果　福辛普利组大鼠心肌超微结构和钙泵功能保持稳定 ,心肌重量和钙含量明显低于安慰剂组 (P<0 .0 5 )。结论　福辛普利不仅能防治心肌肥厚 ,而且能保护肌浆网钙泵功能 ,防止心肌钙超载损伤     

福辛普利联合氢氯噻嗪治疗老年原发性高血压

目的 观察福辛普利联合氢氯噻嗪治疗老年原发性高血压的临床疗效.方法 60例老年原发性高血压病人进行随机分组,治疗组30例,给予福辛普利联合氢氯噻嗪治疗.对照组30例,单用福辛普利治疗,疗程8周,两组进行疗效比较.结果 治疗组总有效率90%,对照组总有效率83%(P<0.05).结论 福辛普利联合氢氯噻嗪治疗老年原发性高血压,疗效优于单用福辛普利.     

辛伐他汀对人脐静脉内皮细胞血管细胞粘附分子表达的影响

观察辛伐他汀对人脐静脉内皮细胞血管细胞粘附分子1和细胞间粘附分子1表达的影响。采用免疫细胞化学及Westem blot蛋白印迹方法，观察促炎症因子肿瘤坏死因子α和白细胞介素1β对体外培养的人脐静脉内皮细胞中血管细胞粘附分子1和细胞间粘附分子1表达的影响，并以辛伐他汀干预，观察其对上述作用的影响。结果发现，肿瘤坏死因子α和白细胞介素1β明显增加人脐静脉内皮细胞中血管细胞粘附分子1和细胞间粘附分子1的表达，辛伐他汀可一定程度抑制上述作用。结果提示，辛伐他汀一定程度抑制促炎症因子刺激导致的细胞粘附分子表达上调，可能具有增加粥样斑块稳定性和延缓动脉粥样硬化进程的作用。     

复方丹参滴丸及其与福辛普利联用对高血压大鼠心肌细胞凋亡的影响

目的探讨复方丹参滴丸(DSP)及其与福辛普利联用对自发性高血压大鼠(SHRs)心肌细胞凋亡的影响.方法将48只8周龄雄性SHRs随机分为6组:DSP小剂量组、DSP大剂量组、福辛普利组、DSP小剂量与福辛普利联用组、DSP大剂量与福辛普利联用组、SHRs对照组.6组分别干预8周后测大鼠尾动脉收缩压;SHRs左心室细胞凋亡率及凋亡相关基因蛋白表达;电镜下心肌组织超微结构.结果与对照组比较DSP可明显降低心肌细胞凋亡率(P<0.01或P<0.05),并与福辛普利联用时可进一步提高后者的抗左室肥厚与心肌细胞凋亡效应(P<0.01或P<0.05).结论 DSP及其与福辛普利联用可改善SHRs左室心肌细胞凋亡.     

灯盏花素逆转自发性高血压大鼠心室重塑的实验研究

本研究应用灯盏花素和福辛普利干预自发性高血压大鼠 (ＳＨＲ)心肌细胞凋亡 ,从而逆转ＳＨＲ心肌肥厚和心室重塑 ,以期为临床防治高血压及其靶器官损害提供新的策略。1　材料与方法选 10月龄ＳＨＲ18只 (雌、雄各半 ) ,按性别、体重和初始收缩压配对分为 3组 ,分别给予灯盏花素注射液 (灯盏花素组 )、福辛普利注射液 (福辛普利组 )和生理盐水 (对照组 )治疗 8周。用鼠尾容积法监测ＳＨＲ在清醒状态下的尾部收缩压和心率。以左心室湿重 /体重 (ＬＶＷ /ＢＷ ,ｍｇ/ｇ)计算左心室心肌肥厚指数。用改良的ＴＵＮＥＬ法检测心肌凋亡细胞并作半定…     

脑出血患者血肿周围组织的急性炎性损害

目的 了解患者脑出血后急性期血肿周围组织的炎性损害情况。方法选择急性脑出血患者10例,于发病当日或次日行血肿清除术,利用术中所获的出血周围组织碎块进行研究。对照组为2例车祸死亡者。所有标本均作苏木精-伊红(HE)染色,并用免疫组化方法检测血管间黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)的表达情况。结果急性脑出血患者血管周围组织表现出明显的血管源性水肿,有大量中性粒细胞、淋巴细胞浸润。所有病例ICAM-1表达呈阴性,2例脑出血患者VCAM-1表达阳性,主要位于神经元、小胶质细胞和部分小血管内皮。未发现有“白细胞栓”阻塞微血管现象。结论脑出血急性期血肿周围组织存在炎性细胞浸润,以中性粒细胞、淋巴细胞为主。VCAM-1表达于部分患者的神经元、小胶质细胞和小血管内皮。     

依那普利,福辛普利对自发性高血压大鼠心肌超微结构逆转的实验研究

目的：观察血管紧张素ｅｎａｌａｐｒｉｌ和ｆｏｓｉｎｏｐｒｉｌ对ＳＨＲ心肌超微结构的逆转作用。方法：将１０月１８只ＳＨＲ随机分为Ｅｎａｌａｐｒｉｌ（ＳＨＲＥ）、Ｆｏｓｉｎｏｐｒｉｌ（ＳＨＲＦ）和生理盐水（ＳＨＲＣ）三组,给药剂量为１０ｍｇ／ｋｇ／ｄ腹脸内注射８周。测定血压、心室重量指数,电镜观察心肌超微结构改变。结果：两药物组心室肥厚均不同程度消退,部分逆转心肌超微结构改变,而且Ｆｏｓｉｎｏｐｒｉｌ     

福辛普利、氯沙坦对自发性高血压大鼠脂肪组织脂联素的影响

目的：探讨福辛普利和氯沙坦对自发性高血压（SHR）大鼠脂肪组织脂联素的影响。方法：22周龄SHR大鼠随机被分成四组．分别予福辛普利、氯沙坦、福辛普利加氯沙坦、安慰剂喂养。同系魏凯氏（WKY）大鼠作对照组。8周后取尿检测大鼠尿微量蛋白（Upro）和n-乙酰β-d-氨基葡萄糖苷酶（NAG）含量,取脂肪组织用免疫组化法及逆转录聚合酶链式反应（RT-PCR）检测脂联素的mRNA的表达。结果：SHR大鼠脂肪组织脂联素表达较WKY大鼠降低;Upro和NAG酶水平升高（P均〈0．01）;福辛普利组和氯沙坦组与SHR组比较血压降低（P〈0．01）;Upro和NAG酶水平降低（P〈0．01）,脂联素表达上调（P〈0．01）。结论：（1）SHR大鼠Upro和NAG酶水平升高．脂肪组织脂联素表达下调;（2）福辛普利和氯沙坦可以提高SHR大鼠脂肪组织脂联素表达,降低Upro和NAG酶水平。     

Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney

Background

In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney.

Methods

Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry.

Results

Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals.

Conclusion

Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats.     

Eph A2基因与大肠腺癌的关系及机制的研究

目的 探讨Eph A2基因在大肠腺癌转移中的作用及机制.方法 采用免疫组化（SP）技术对126例大肠腺癌组织和相应正常大肠黏膜组织中Eph A2蛋白表达进行检测;并同时测定血清ICAM-1和VCAM-1.结果 Eph A2蛋白表达在126例癌组织中明显高于正常大肠黏膜组织（P＜0.001）,Eph A2蛋白表达阳性患者中血清ICAM-1和VCAM-1均高于Eph A2表达阴性患者,亦高于正常对照组,差异有统计学意义（P＜0 05）.结论 Eph A2基因可能与大肠腺癌的发生、肿瘤细胞的迁移和浸润能力有关,其调节肿瘤细胞转移的机制可能与ICAM-1和VCAM-1有关.     

Inhibition of lymphocyte adhesion to cytokine-activated synovial fibroblasts by glucocorticoids involves the attenuation of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 gene expression

Objective. The aim of this study was to evaluate the ability of glucocorticoids to inhibit lymphocyte adhesion to human synovial fibroblasts. Methods. Adhesion of lymphocytes to cultured synovial fibroblasts was measured by counting the number of cells bound to fibroblasts. Surface expression of intercellular adhesion molecule 1 (ICAM-1) was measured by enzyme-linked immunosorbent assay, while vascular cell adhesion molecule 1 (VCAM-1) surface expression was measured by flow cytometry. ICAM-1 and VCAM-1 messenger RNA (mRNA) levels were assessed by Northern blot analysis. Results. Stimulation of synovial fibroblasts by the proinflammatory cytokines tumor necrosis factor α, interleukin-1β, and interferon-γ resulted in a dose-dependent increase in lymphocyte adhesion to synovial fibroblasts. This response was inhibited by preincubation of the cells with the synthetic glucocorticoid dexa-methasone. Since lymphocyte adhesion to synovial fibroblasts is known to be mediated by VCAM-1 and ICAM-1, we examined the modulation of VCAM-1 and ICAM-1 expression in these cells. All 3 cytokines stimulated VCAM-1 and ICAM-1 surface and mRNA expression. Dexamethasone inhibited both VCAM-1 and ICAM-1 surface and mRNA expression in a dose-dependent manner, which correlated with the inhibition of lymphocyte adhesion. Conclusion. Taken together, these results suggest that glucocorticoids may reduce inflammatory responses at extravascular sites by inhibiting the expression of these adhesion molecules, thereby reducing the adhesion of lymphocytes to connective tissue cells.     

Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats

Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/?)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/?)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage.     

自发性高血压大鼠血管壁脂联素的表达及其意义

目的：探讨自发性高血压大鼠（SHR）血管壁脂联素的的表达和福辛普利、氯沙坦对其表达的影响。方法：22周龄20只SHR大鼠随机被分成四组：福辛普利干预组、氯沙坦干预组、福辛普利加氯沙坦干预组、安慰剂喂养组。5只同系魏凯氏（WKY）大鼠做对照组。8周后取尿检测大鼠24h尿蛋白（Upro）和n-乙酰β—d-氨基葡萄糖苷酶（NAG）．取脂肪组织中血管壁用免疫组化法检测脂联素的表达。结果：SHR大鼠脂肪血管壁脂联素表达较正常对照的WKY大鼠降低，Upro和NAG酶水平升高（P均〈0．01），福辛普利组和氯沙坦组与SHR组比较血压降低（P〈0．01）．Upro和NAG酶水平降低（P均〈0．01），血管壁脂联素表达上调（P〈0．01）。结论：（1）SHR大鼠Upro和NAG酶水平升高，脂肪组织血管壁脂联素表达下调；（2）福辛普利和氯沙坦可以提高SHR大鼠脂肪组织血管壁脂联素表达，降低Upro和NAG酶水平。     

Junctional adhesion molecule-1 is upregulated in spontaneously hypertensive rats: evidence for a prohypertensive role within the brain stem

Junctional adhesion molecule-1 (JAM-1) forms part of the tight junction between adjacent endothelial cells. Using microarray technology, we showed previously that JAM-1 was differentially expressed in the brain stem of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto (WKY) rats. In this study, we quantified the expression of JAM-1 in the brain stem of spontaneously hypertensive rats and WKY rats and established whether any differential expression was confined to this region of the brain or was ubiquitous throughout the central nervous system and, indeed, the whole body. Because the nucleus tractus solitarii plays a pivotal role in arterial pressure regulation, we assessed whether JAM-1 in this region affects the chronic regulation of arterial pressure. Real time RT-PCR revealed that JAM-1 mRNA was upregulated in multiple regions of the brain and all of the peripheral vascular beds studied. In the nucleus tractus solitarii, the level of JAM-1 mRNA was significantly higher in both young (3-week-old, prehypertensive) and adult male spontaneously hypertensive rats (15 to 18 weeks old) than that of age-matched WKY rats (fold differences; prehypertensives: 1.01+/-0.06 versus 1.59+/-0.13; n=10; P<0.01; adult: 1.08+/-0.14 versus 2.86+/-0.57; n=10; P<0.01). After adenoviral-mediated expression of JAM-1 in the nucleus tractus solitarii of adult WKY rats (15 weeks old; n=6), systolic pressure was increased from 120+/-4 to 132+/-4 mm Hg (P<0.01). Our data suggest that JAM-1 expression in the spontaneously hypertensive rat is upregulated throughout the body compared with the WKY rat and that this is not secondary to the hypertension. When JAM-1 is expressed in the nucleus tractus solitarii, it raises arterial pressure, suggesting a novel prohypertensive role for this protein within the brain stem.