尼群地平与卡托普利对高血压鼠肾血管功能的保护作用

目的：比较尼群地平与卡托普利对高血压鼠肾血管功能的保护作用。方法：离体肾灌注试验１４周龄自发性高血压大鼠（ＳＨＲ）。结果：肾血管对去甲肾上腺素（ＮＥ）及氯化钡呈超常的收缩反应，２８周龄ＳＨＲ的超常收缩反应更为明显。但于１４周龄服用尼群地平（３０ｍｇ／ｋｇ·ｄ－１）或卡托普利（５０ｍｇ／ｋｇ·ｄ１）降压治疗１４周后ＳＨＲ，其肾血管收缩反应明显弱于对照的同龄ＳＨＲ，并接近同龄的正常血压ＷＫＹ大鼠。结论：尼群地平或卡托普利有效降压，并可逆转ＳＨＲ肾血管对缩血管物质的超常收缩反应，且两药的效应相当     

内皮素A受体拮抗剂BQ123降压作用的研究

为探讨内皮毒在机体血压调节中的意义，本文观察ＥＴＡ受体拮抗剂ＢＱ１２３的降压作用。静脉注射ＢＱ１２３（０．１，１和２ｍｇ／ｋｇ）后，自发性高血压大鼠（ＳＨＲ）和正常血压大鼠（ＷＫＹ）血压呈剂量依赖地降低，持续４０～６０分钟。ＢＱ１２３对ＳＨＲ的降压作用强于ＷＫＹ。给Ｗｉｓｔａｒ大鼠静脉注射ＢＱ１２３呈剂量依赖地拮抗外源性ＥＴ－１（２×１０＾－９ｍｏｌ／ｋｇ）引起的血压升高反应。在培养的ＳＨＲＢＱ１     

酮康唑连续给药对犬肝毒性的病理学观察

为了更深入地研究酮康唑对肝的毒性损害，采用杂种犬作了为期一个月的长期毒性实验，分别用电镜和光镜技术对犬的肝进行了细胞超微结构和病理组织学观察。实验设３个剂量组，给药剂量为大剂量组７０ｍｇ／（ｋｇ．ｄ），中剂量组３５ｍｇ（ｋｇ．ｄ），小剂量组为１７．５ｍｇ（ｋｇ．ｄ），另一组为溶煤对照组，连续灌胃３０天。     

高血压冠状动脉平滑肌细胞的形态学变化

既往研究表明,高血压伴随有血管壁中层血管平滑肌细胞（ＶＳＭＣ）的肥大〔１,２〕。但是高血压未形成时冠状动脉中层ＶＳＭＣ是否已存在肥大及抗高血压药物对ＶＳＭＣ肥大的影响尚不清楚。本研究以自发性高血压大鼠（ＳＨＲ）和同种系正常血压的京都种大鼠（ＷＫＹ）为动物模型,通过观察ＳＨＲ高血压形成前后及抗高血压药物罗沙坦治疗后,左冠状动脉前降支中层ＶＳＭＣ的形态变化,了解高血压冠状动脉ＶＳＭＣ的形态学变化及抗高血压药物治疗对其的影响。１　材料和方法１１　实验动物及分组　雄性ＳＨＲ和ＷＫＹ由上海市高血压研究所…     

银杏叶提取物(EGb761)对自发性高血压大鼠的治疗作用及其机理的实验研究

目的银杏叶提取物（ＥＧｂ７６１）对改善和治疗心脑血管疾病具有明显作用。本研究探讨ＥＧｂ７６１对自发性高血压大鼠（ＳＨＲ）的治疗作用,并通过对脑微循环功能的影响,探讨其作用机理。方法自发性高血压大鼠（ＳＨＲｎ一２０）及正常血压Ｗｉｓｔａｒ大鼠（ｎ—２０）分别分成治疗组和对照组,经口分别给予１００ｍｇ／ｋｇ／ｄ的ＥＧｂ７６１（Ｔａｎａｋａｎ）和安慰剂,经１０ｄ治疗后,进行血压、脑微循环血流量、微血管自律运动以及循环内皮细胞计数等参数的测量。结果 ＥＧｂ７６１对ＳＨＲ治疗组具有明显的降压作用（ＰＭＯ．０１）,并明显增加微循环血流量（Ｐ＜０．０５）。此外ＳＨＲ经ＥＧｂ７６１治疗后,微血管自律运动的振幅显著改善,呈低频高幅状态,循环内皮细胞计数显著降低（Ｐ＜０．０５）。结论 实验结果表明ＥＧｂ７６１具有明显降低自发性高血压大鼠血压的作用,以及明显改善脑微循环功能。待别是改善微血管自律运动状态,对血管内皮也具有显著保护作用。上述结果提示ＥＧｂ７６１对微循环功能的改善及对微血管自律运动的加强是其降压作用的重要机理之一。     

SHR心肌细胞离子泵活性与血压及左心室肥厚的相？…

目的：研究心肌细胞膜离子泵活性与血压及左心室肥厚之间的关系。方法：将１２只自发性高血压大鼠（ＳＨＲ）分成两组,一组灌喂缬沙坦（２４ｍｇ／ｋｇ）,另一组和６只正常大鼠（ＷＫＹ）灌喂生理盐水共４周。测量实验前后及实验后心肌细胞膜的Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶、Ｃａ＾＋－ＡＴＰ酶和Ｍｇ＾２＋－ＡＴＰ酶活性,同时测量心肌细胞横径（ＴＤＭ）和心脏重量／体重（ＨＷ／ＢＷ）。结果：ＳＨＲ生理盐水组的血压和ＴＤＭ及     

阈下剂量氯胺酮复合丙泊酚用于人工流产术的临床研究

目的 探讨阈下剂量氯胺酮复合丙泊酚用于人工流产术的麻醉效果及其对呼吸、循环功能的影响。方法 １８０例ＡＳＡⅠ～Ⅱ级择期人工流产病人,随机分成两组各９０例,Ⅰ组丙泊酚３ｍｇ／ｋｇ,Ⅱ组氯胺酮０．４ｍｇ／ｋｇ加丙泊酚２ｍｇ／ｋｇ,术中视病人反应及手术时间追加丙泊酚３０ｍｇ～５０ｍｇ,记录注药前、注药后２ｍｉｎ、５ｍｉｎ的血压、心率、呼吸变化和丙泊酚用量。结果 注药后２ｍｉｎＳＢＰ、ＤＢＰ、ＨＲ达到最大降幅,分别下降：Ⅰ组２２％、２３％、２６％,Ⅱ组１２％、１５％、１９％,两组同期值比较有显著性差异（ｐ〈０．０１）。Ⅱ组丙泊酚用量接近Ⅰ组的半量（ｐ〈０．０１）。结果表明阈下剂量氯胺酮具有明显镇痛作用,和丙泊酚的催眠作用明显协同,能降低丙泊酚的诱导剂量和减轻丙泊酚对循环抑制作用。结论 阈下剂量氯胺酮复合丙泊酚是人工流产     

肝细胞刺激物质对感染鸭乙型肝炎病毒的雏鸭体内抗病毒作用的实验研究

以感染鸭乙型肝炎病毒（ＤＨＢＶ）的北京雏鸭为体内实验动物模型，观察了肝细胞刺激物质（ＨＳＳ）对鸭乙型肝炎病毒的抗病毒作用。１日龄北京鸭实验感染ＤＨＢＶ，７天后血清ＤＨＢＶＤＮＡ阳性，给予药物治疗１０天，用斑点杂交方法检测用药前后血清ＤＨＢＶＤＮＡ，分析药物对血清ＤＨＢＶＤＮＡ是否有抑制作用，结果显示：ＨＳＳ大、小两个剂量组（分别为５０ｍｇ／ｋｇ／ｄ和２００ｍｇ／ｋｇ／ｄ）均对ＤＨＢＶＤＮＡ有抑制作用，大剂量组出现ＤＨＢＶＤＮＡ抑制作用时间早于小剂量组，用药５天、１０天及停药３天血清ＤＨＢＶＤＮＡ中位抑制率显著高于生理盐水对照组（Ｐ＜０．０５）；两个剂量组均无停药反跳；生理盐水组用药前后ＤＨＢＶＤＮＡ的Ａ值比较差异无显著性意义（Ｐ＞０．０５）。停药后３天肝组织病理光镜及电镜均显示ＨＳＳ组病变较生理盐水组轻。结论：肝细胞刺激物质有一定的保肝和抑制ＤＨＢＶＤＮＡ复制的作用     

糖尿病大鼠腹主动脉的在体顺应性和弹性模量

目的探讨糖尿病大动脉生物力学特性重建以及与高血压、高血糖的关系。方法以ＳＴＺ诱导ＳＨＲ大鼠和ＳＤ大鼠分别建立伴有（ＳＨＲＤＭ组）和不伴有（ＳＤＤＭ组）高血压的糖尿病动物模型,对其腹主动脉的在体顺应性和弹性模量进行研究。结果糖尿病４周开始出现顺应性降低。ＳＨＲＤＭ组从４周起、ＳＤＤＭ组从８周起,出现Ｅｐ、Ｅv和Ｅｉｎｃ增加,增幅随病程而增大,ＳＨＲＤＭ组的增幅大于ＳＤＤＭ。结论腹主动脉各力学特性参数中,顺应性改变最早,可作为评价血管功能的敏感指标。高血糖和高血压均可使Ｅｐ增大,高血糖的作用大于高血压。     

糖尿病大鼠腹主动脉的在体顺应性和弹性模量

目的探讨糖尿病大动脉生物力学特性重建以及与高血压、高血糖的关系。方法以ＳＴＺ诱导ＳＨＲ大鼠和ＳＤ大鼠分别建立伴有（ＳＨＲＤＭ组）和不伴有（ＳＤＤＭ组）高血压的糖尿病动物模型,对其腹主动脉的在体顺应性和弹性模量进行研究。结果糖尿病４周开始出现顺应性降低。ＳＨＲＤＭ组从４周起、ＳＤＤＭ组从８周起,出现Ｅｐ、Ｅv和Ｅｉｎｃ增加,增幅随病程而增大,ＳＨＲＤＭ组的增幅大于ＳＤＤＭ。结论腹主动脉各力学特性参数中,顺应性改变最早,可作为评价血管功能的敏感指标。高血糖和高血压均可使Ｅｐ增大,高血糖的作用大于高血压。     

氯沙坦逆转高血压大鼠心肌重塑的实验研究

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌重塑的影响。方法16周龄雄性SHR20只,随机分为氯沙坦治疗组和SHR对照组。同龄雄性WKY鼠10只作为正常对照组。给予氯沙坦每天30mg/kg溶于饮水灌胃治疗17周。测定动脉收缩压、左心室壁的厚度、左心室重量与体重之比(LVW/BW)。透射电镜评估左心室肥厚(LVH)的程度。用真彩色图像分析系统计算左心室胶原容积分数。结果氯沙坦治疗组血压、LVW/BW、左室壁厚度与SHR对照组相比明显降低,但与WKY相比有所升高。透射电镜下氯沙坦治疗组心肌的超微结构与WKY相似,SHR的结构有异常改变。与SHR对照组相比,氯沙坦治疗组左心室胶原容积分数下降。结论氯沙坦能有效地降低SHR的血压、逆转高血压左室重塑。     

血管紧张素Ⅱ在自发性高血压大鼠主动脉重建中的作用

目的:探讨血管紧张素Ⅱ(AngⅡ)在高血压主动脉重建中的作用。方法:选用AngⅡ受体I亚型拮抗剂losartan,对雄性自发性高血压大鼠(SHR)进行为期10周的治疗,观察并比较其在剂量15 mg/kg·d^-1及0.75 mg/kg·d-1时,对16周到26周SHR胸主动脉重建的影响。结果:Losartan 15 mg在降低血压的同时, 通过抑制主动脉中膜平滑肌细胞(VSMC)的肥大明显抑制了主动脉肥厚,losartan 0.75 mg未能使血压下降的情况下,对VSMC及主动脉肥厚均没有影响。Losartan对胶原纤维的作用与对VSMC的作用不同,两种剂量的losartan均明显抑制了胶原纤维的合成。结论:AngⅡ对SHR主动脉平滑肌生长的调节可能为压力依赖性,对胶原纤维的作用则可能是通过非压力机制。     

氯沙坦逆转高血压大鼠阻力血管重塑的实验研究

目的:探讨氯沙坦对自发性高血压大鼠(SHR)阻力血管重塑的影响。方法:将雄性SHR20只随机分为氯沙坦治疗组和SHR对照组。另选同系雄性WKY大鼠10只作为正常对照组。治疗组给予氯沙坦30mg/kg/天,溶于饮水灌胃治疗17周。颈动脉插管,心电血流动力学监护仪测定动脉收缩压,应用计算机图像分析,计算血管壁腔面积比,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化;血浆放免法测肾素活性和血管紧张素Ⅱ(AngⅡ)含量。结果:氯沙坦治疗组的血管壁腔面积比与SHR对照组相比有所降低(P<0.05),但与WKY相比有所升高(P<0.05);血浆肾素活性在WKY组和SHR对照组之间无明显差异(P>0.05),治疗组肾素活性高于SHR对照组(P<0.05);治疗组的AngⅡ水平高于SHR对照组(P<0.01)。结论:氯沙坦具有逆转SHR血管重塑的作用。     

氯沙坦对自发性高血压大鼠左心室肥厚和转化生长因子β_1的影响

目的 :探讨转化生长因子 β1 (TGFβ1 )在自发性高血压大鼠(SHR)左心室肥厚中的作用及氯沙坦对左心室肥厚和TGFβ1 水平的影响。方法 :2 0只SHR随机分成氯沙坦治疗组和未治疗组 ,每组10只 ,用免疫组织化学法检测SHR心肌TGFβ1 的表达及氯沙坦治疗后的改变 ,同时观察心肌肥厚的变化 ,并与正常WKY组对照。结果 :正常组心肌细胞胞浆内TGFβ1 表达呈弱阳性 ,SHR对照组呈强阳性 ,氯沙坦治疗组呈阳性反应。用图像分析仪计算其平均吸光度分别为 17.46± 2 .3 8、15 6.81± 2 1.75、67.19± 7.2 4,并且SHR左心室质量指数 (LVWI)高于WKY组 ,氯沙坦治疗组LVWI低于对照组。结论 :TGFβ1 在自发性高血压大鼠心肌中表达增强 ,而氯沙坦治疗可抑制其表达 ,从而可能延缓SHR左心室肥厚的病理学进展。     

Hypertensive brain damage: comparative evaluation of protective effect of treatment with dihydropyridine derivatives in spontaneously hypertensive rats

Hypertension is the main risk factor for cerebrovascular disease including vascular dementia and control of blood pressure might protect from lesions causing cognitive impairment. The influence of anti-hypertensive treatment on hypertensive brain damage was assessed in spontaneously hypertensive rats (SHR). SHR and age-matched normotensive Wistar Kyoto (WKY) rats were treated from the 14-26th week of age with the dihydropyridine-type Ca2+ channel blockers lercanidipine, manidipine and nimodipine and as a reference with the non-dihydropyridine-type vasodilator hydralazine. Volume of brain areas, number of nerve cells and glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 kDa immunoreactivity were investigated in frontal and occipital cortex and in hippocampus. In control SHR, systolic blood pressure (SBP) was significantly higher in comparison with WKY rats. Compounds tested decreased to a similar extent SBP values in SHR, with the exception of nimodipine that caused a smaller reduction of SBP compared with other compounds. Decreased volume and number of nerve cells and loss of neurofilament protein immunoreactivity were observed in SHR. GFAP-immunoreactive astrocytes increased in number (hyperplasia) and in size (hypertrophy) in the frontal and occipital cortex of control SHR, and only in number in the hippocampus. Anti-hypertensive treatment countered in part microanatomical changes occurring in SHR. Drugs investigated with the exception of nimodipine exerted an equi-hypotensive effect. In spite of this the best protection was exerted by lercanidipine and, to a lesser extent, by nimodipine. Compared with nimodipine, lercanidipine induced a more effective decrease of SBP. This may represent an advantage in the treatment of hypertension with risk of brain damage.     

坎沙曲联合缬沙坦与奥帕曲拉均减轻大鼠心肌肥厚

目的比较坎沙曲联合缬沙坦与奥帕曲拉(OMA)对大鼠心肌肥厚的保护作用。方法注射1 mg/kg异丙肾上腺素(ISO)制备大鼠心肌肥厚模型,随机分为对照组、心肌肥厚组、坎沙曲组、缬沙坦组、OMA组与坎沙曲+缬沙坦(半量及全量)组,每组n=8,染色后测定心肌细胞横截面积、心肌间质胶原容积分数及血管周围胶原面积;免疫组化学检测心肌组织p-PI3K和p-Akt表达;放免法测定血浆血管紧张素Ⅱ(AngⅡ)、心房利钠肽(ANP)、缓激肽(BK)水平。结果 1)坎沙曲+缬沙坦(全量)及OMA组均可降低心肌肥厚组大鼠心脏重量指数(分别为3.64±0.30、3.62±0.28和4.32±0.58)、心肌细胞横截面积、心肌间质胶原容积分数及血管周围胶原面积的明显上升(P<0.01),两组间无明显差异。2)与心肌肥厚组相比,坎沙曲+缬沙坦(全量)及OMA组均可降低血浆AngⅡ含量[分别为(741±89)、(682±66)和(479±62)ng/L],并显著上调ANP[分别为(117±33)、(298±91)和(288±95)μg/L]及BK[分别为(124±12)、(232±21)和(309±24)ng/L]水平(P<0.01),但坎沙曲+缬沙坦(全量)较OMA组BK的上调幅度低。3)坎沙曲+缬沙坦(全量)与OMA均下调心肌肥厚组心肌组织p-PI3K和p-Akt蛋白表达,且两者间无明显差异。结论坎沙曲联合缬沙坦与OMA均可减轻大鼠心肌肥厚,但对血浆激素水平的影响有差异。     

Influence of treatment with Ca(2+) antagonists on cerebral vasculature of spontaneously hypertensive rats

Hypertension is the main cause of stroke that represents the second most common cause of death in the industrialized world and a leading cause of inability of the elderly. Lowering blood pressure reduces cerebrovascular morbidity and mortality, but it is still controversial if blood pressure should be lowered in elderly individuals with concomitant cerebrovascular disease. The present study has analyzed comparatively the effect of treatment with the dihydropyridine-type Ca(2+) channel blockers lercanidipine, manidipine and nimodipine and with the non dihydropyridine-type vasodilator hydralazine on hypertension-dependent cerebrovascular changes in spontaneously hypertensive rats (SHR). Analysis included medium and small sized pial arteries and intracerebral arteries of frontal cortex, hippocampus, striatum, and cerebellum. In control SHR, systolic pressure (SBP) values were significantly higher in comparison with WKY rats. Pharmacological treatment significantly decreased SBP values, with nimodipine reducing only moderately SBP. In control SHR, thickening of arterial wall accompanied by luminal narrowing with consequent increase of the wall-to-lumen ratio occurred both in pial and intracerebral arteries. Dihydropyridine-type Ca(2+) antagonists and to a lesser extent hydralazine countered these morphological alterations. Lercanidipine displayed a particular activity on small sized intraparenchymal brain arteries, where it was more effective than other compounds tested. This activity of lercanidipine on small-sized intracerebral arteries might represent an interesting property for the treatment of hypertensive brain damage with concomitant ischemia.     

Lithium chloride stabilizes systolic blood pressure and increases adrenal catecholamines in the spontaneously hypertensive rat

The effects of daily, intraperitoneal injections of LiCl (3 mEq/kg) on systolic blood pressure (SBP) and adrenal catecholamine levels were measured in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Control animals from each strain were injected with equivalent volumes (0.1 ml/100 g b.wt.) of 0.9% saline (0.15 mEq/kg). SBP in LiCl-treated SHR was significantly lower (p less than 0.05) than that of saline-treated SHR (177 +/- 7 vs. 196 +/- 4 mm Hg, respectively) after one week. After two weeks SBP was lower in LiCl SHR than in saline controls, but this difference was not significant. While SBP of both LiCl and saline treated WKY was not significantly different (146 +/- 4 vs. 147 +/- 8 mm Hg, respectively), SBP in both WKY groups remained lower than the SBP for either group of SHR. LiCl induced a significant weight loss in the SHR, but not in the WKY. Adrenal norepinephrine and epinephrine were significantly (p less than 0.05) higher in LiCl-treated rats of both strains; dopamine was also higher in LiCl-treated rats of both strains, but significant only between SHR-LiCl and SHR controls. It appears that LiCl's effect in slowing the development of hypertension is independent of its action on adrenal catecholamines. The SHR's increased sensitivity to LiCl, relative to weight loss and SBP, may reflect differences in genetic or physiological status of the animal compared to WKY. These differences may be associated with alterations in membrane ion transport systems.     

氯沙坦对自发性高血压大鼠血管紧张素Ⅱ及炎症因子的影响

目的观察血管紧张素Ⅱ（AngⅡ）的AT-1型受体阻断剂氯沙坦对自发性高血压大鼠（SHR）血清AngⅡ及炎症因子水平的影响。方法应用ELISA试剂盒检测SHR（n=12）和血压正常大鼠（WKY）（n=6）血清中AngⅡ的水平及炎症因子IL-1β、IL-6和高敏C反应蛋白（hsCRP）的浓度。结果 SHR血清中AngⅡ、IL-1β、IL-6及hsCRP水平明显升高,与WKY的相应指标比较差异均具有统计学意义（P值均〈0.05）。氯沙坦在降低SHR血压的同时可以明显地降低其血清中AngⅡ、IL-1β、IL-6及hsCRP的水平,与用药前的相应指标比较差异均具有统计学意义（P值均〈0.05）。结论氯沙坦可以降低SHR血清的AngⅡ及炎症因子IL-1β、IL-6和hsCRP的水平,这可能是氯沙坦的降压机制之一。     

氯沙坦对自发性高血压大鼠主动脉内膜ICAM-1和PAI-1表达的影响

目的 :比较早期雄性自发性高血压大鼠 (SHR)和正常雄性同周龄WistarKyoto大鼠 (WKY)主动脉内膜细胞间粘附分子 1(ICAM 1)和纤溶酶原激活物抑制剂 1(PAI 1)的表达及氯沙坦对其的影响。方法 :将 2 0只雄性SHR随机分成二组 ,每组 10只 ,其中一组灌喂氯沙坦 2 0mg/kg/天 ,另一对照组给正常饮水 ,共 12周 ,并与WKY 10只比较。采用免疫组织化学方法检测三组大鼠主动脉内膜ICAM 1和PAI 1的表达。结果 :与WKY大鼠比较 ,SHR对照组主动脉内膜ICAM 1和PAI 1表达明显增高 ;经氯沙坦治疗 12周后SHR血压显著降低 ,主动脉内膜ICAM 1和PAI 1表达亦明显下降。结论 :氯沙坦在有效降压的同时也明显抑制SHR主动脉内膜ICAM 1和PAI 1的表达 ,提示氯沙坦作为血管紧张素II受体 1拮抗剂 (AT1 R)在抗高血压并发症发生中起一定的作用