菊藤胶囊对应激性高血压大鼠血压及血液ET、NO含量的影响

目的:探讨了菊藤胶囊对应激性高血压(SIH)大鼠血压影响的可能机制。方法:采用电击足底应激刺激的方法制备应激性高血压大鼠模型,观察每天应激刺激前灌服菊藤胶囊对应激大鼠血压的影响,检测血清一氧化氮(NO)、血浆内皮素(ET)水平。结果:模型组血压显著升高,模型组与其它各组血压比较差异均有统计学意义(P<0.01)。正常组、卡托组、菊高组之间进行比较,差异无统计学意义(P>0.05);与模型组比较,菊藤胶囊高中剂量组、西药组可使SIH血清NO水平显著升高(P<0.01),高中剂量组、西药组可使血浆ET水平显著下降(P<0.01);正常组、西药组、中药高剂量组之间进行比较并无显著性差异。结论:SIH形成与血清NO水平下降、血浆ET水平升高有关,菊藤胶囊能有效降低血压,其降压机制可能与调整血清NO、血浆ET水平有关。     

动脉压力感受性反射受损后血浆和心脏、肾脏组织AngⅡ含量的变化

既往的研究表明,动脉压力感受性反射（ABR）功能下降在高血压靶器官损伤中起独立作用。为进一步研究ABR功能下降致器官损伤的可能机制,实验采用去窦弓神经（SAD）大鼠作为ABR受损的动物模型,分别测定清醒、自由活动状态下SAD及对照的假手术组大鼠24h动脉血压、心率、血压波动性（BPV）及心率波动性（HRV）。并采用放免法测定血浆、心脏和肾脏组织的血管紧张素Ⅱ（AngⅡ）含量。结果发现,SAD术后1周大鼠的24h平均收缩压（SBP）、舒张压（DBP）均显著高于对照组及术后18周的慢性期SAD大鼠。SAD术后18周,24h平均SBP、DBP及HR与假手术对照组均无显著差异;24h收缩压波动性（SBPV）和舒张压波动性（DBPV）均显著高于对照组大鼠。SAD大鼠术后1周的血浆、心脏和肾脏组织的AngⅡ含量及术后18周的血浆AngⅡ水平与对照组之间相比无显著差异。而在术后慢性期（18周）,SAD大鼠的心肌及肾组织AngⅡ含量显著高于假手术对照组大鼠。在术后18周时,接受慢性应激刺激的SAD大鼠,其血浆、心肌及肾组织中AngⅡ水平显著高于同处应激状态下的假手术对照组大鼠及未接受应激刺激的SAD大鼠。这些结果表明,SAD术后急性期血压增高,但在慢性期平均血压并无增高,仅BPV增高;慢性期心、肾组织内AngⅡ的分泌增加。在慢性期接受应激可致AngⅡ过度分泌,上述结果提示,BPV增高和心、肾组织AngⅡ含量升高与SAD大鼠发生心脏、肾脏等器官损害有关。     

损毁缰核对应激性高血压形成的影响

目的和方法 :运用核团损毁和微量注射的方法观察损毁缰核 (Hb)对应激性高血压 (SIH)形成进程的影响及SIH大鼠Hb内神经元对L 谷氨酸 (Glu)反应性的变化。结果 :①损毁双侧Hb延缓了SIH的形成进程 ;②在SIH大鼠内侧Hb(MHb)微量注射不同浓度的CIu ,血压明显升高 ,呈浓度依赖性 ,升高值与正常大鼠MHb注入等量GIu引起的升高值相比 ,有显著性差异 (P <0 .0 5 ) ;③在SIH大鼠外侧Hb(LHb)注入不同浓度的Glu ,血压明显下降 ,也呈浓度依赖性 ,下降值与正常大鼠LHb注入等量Glu引起的下降值相比 ,有显著性差异 (P <0 .0 5 )。结论 :损毁Hb延缓了SIH的形成进程 ,SIH大鼠Hb对Glu的敏感性提高了 ,Hb参与SIH的形成 ,且其作用有部位特异性。     

血管紧张素Ⅱ在紧张应激引起大鼠血压升高中的作用

实验在雄性Sprague Dawley大鼠上进行。实验动物被随机分为对照组、应激组和应激 腹腔注射卡托普利 (captopril)组。应激组大鼠每天给予电击足底结合噪声的应激刺激 ,每日 2次 ,每次 2h ,连续 15d ;应激 ipcaptopril组大鼠在给予应激刺激期间 ,经腹腔内注射captopril 5 0mg/kg d。实验结果观察到 ,15d后 ,三组大鼠平均尾动脉收缩压分别为 :对照组 16 32± 0 5 5kPa (n =7) ,应激组 19 75± 1 0kPa (n =8) ,应激 ipcaptopril组17 6 9± 1 0 7kPa (n =8)。应激 ipcaptopril组大鼠的尾动脉收缩压较对照组动物有显著升高 (P <0 0 5 ) ,但又显著低于应激组大鼠 (P <0 0 5 ) ;同时 ,三组大鼠下丘脑组织中AVP mRNA水平分别为 :对照组 7332 6 6± 5 2 2 6 5 (n =6 ) ;应激组 12 990 33± 15 33 5 8(n =6 ) ,应激 ipcaptopril组 10 6 15 5± 1410 49(n =6 )。应激 ipcaptopril组大鼠下丘脑组织中AVP mRNA水平较对照组有显著升高 (P <0 0 0 1) ,但又显著低于单纯应激组大鼠 (P <0 0 5 )。统计结果显示 :各组大鼠下丘脑组织中AVP mRNA水平与血压之间存在正相关关系 (P <0 0 0 1)。对照组大鼠在侧脑室注射 (icv)选择性血管升压素 (AVP)V1受体拮抗剂d(CH2 ) 5Tyr(Me)AVP 0 3μg后 ,其平均动脉压 (     

第四脑室注射吗啡对应激性高血粘度与血压升高的影响

实验用Wistar大鼠99只,雄性250g左右,随机分三组:对照组、悬吊加束缚组、悬吊一束缚加电针组。结果:(1)清醒大鼠束缚加悬吊可引起应激性高血粘度和血压升高,切断双侧颈迷走神经后上述现象仍存在。静脉注射心得安(0.3mg/ml)或酚妥拉明(0.3 mg/ml)对正常大鼠血压、血粘度影响不大,但对应激性血压升高均有抑制作用。静脉注射心得安还可降低应激性高血粘度。(2)电针大鼠右后肢对应激性高血粘度和血压升高有抑制作用。(3)第四脑室内注射吗啡(10μg/10 μl)15或30min后可降低应激性高血粘度和血压升高,注入等量生理盐水无变化。若在第四脑室注射纳洛酮 (10μg/10μl)则可部分阻断电针右后肢对悬吊-束缚诱发的高血粘度和血压升高的抑制作用。结果提示:悬吊-束缚大鼠可能兴奋交感神经传出系统经激活β受体诱发应激性高血粘度阻断α或β受体可降低应激性血压升高。脑内阿片肽可抑制应激性高血粘度和血压升高,脑内河片肽受体的激活可参与电针后肢对应激性高血粘度和血压升高的抑制作用。     

血管紧张素Ⅱ上调自发性高血压大鼠和Wistar-Kyoto大鼠血管平滑肌细胞外信号调节激酶的信号转导

本文研究血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)和Wistar- Kyoto(WKY)大鼠血管平滑肌细胞(vascular smooth muscle cells．VSMCs)细胞外信号调节激酶(extracellular signal-regulated pro- tein kinases,ERKs)信号途径的影响。体外培养SHR和WKY大鼠的VSMCs,先在培养基中加入终浓度为1×105mmol／L 的缬沙坦或1×105mmol／L的PD98059或不加药物,再给予1×107mmol／L的Ang Ⅱ刺激24 h后收集细胞,以无血清培养基 培养的VSMCs作对照。用免疫沉淀法测定ERK活性;用Western-blot方法检测总ERK(total ERK,t-ERK)、磷酸化ERK (phosphorylated-ERK,p-ERK)及丝裂素活化蛋白激酶磷酸酶-1(mitogen-activated protem kinases phosphatase-1,MKP-1)水 平;用RT-PCR法半定量测定MKP-1 mRNA的含量。结果显示:(1)SHR和WKY大鼠Ang Ⅱ刺激组VSMCs中ERK活 性、p-ERK、MKP-1及MKP-1 mRNA水平均明显高于对照组(P<0．05);SHR和WKY大鼠Ang Ⅱ+缬沙坦组和Ang Ⅱ +PD98059组的上述指标与对照组比较均无显著性差异。(2)SHR大鼠VSMCs中ERK活性、P-ERK、MKP-1及MKP-1 mRNA均显著高于相同干预的WKY大鼠(P<0．01)。(3)SHR和WKY大鼠之间以及对照组、Ang Ⅱ刺激组、Ang Ⅱ+缬沙 坦组和Ang Ⅱ+PD98059组间VSMCs中t-ERK水平均无显著性差异。以上结果表明,Ang Ⅱ可能主要通过其1型(Ang Ⅱ type 1,AT)受体激活SHR和WKY大鼠VSMCs中ERK途径,增加ERK活性和p-ERK蛋白水平,继而引起MKP-1及 MKP-1 mRNA水平升高。     

中脑导水管周围灰质NO在应激大鼠高血压形成中的作用及其机制探讨

目的：探讨大鼠中脑导水管周围灰质（PAG）内NO在应激性高血压（SIH）发病中的作用。方法：采用电击足底结合噪声建立应激性高血压大鼠模型,NADPH－d组化方法显示PAG内一氧化氮合酶（NOS）阳性神经元的变化,核团微注法和放免法检测PAG内微量注射L－NNA对动物血压和延髓头端腹外侧区（RVLM）内Ach含量的影响。结果：（1）应激性高血压大鼠血压升高,PAG背外侧区NOS阳性神经元数量明显减少,平均灰度值增高,且RVLM内Ach含量也增多。（2）PAG内微量注射L－NNA 100mmol/L 0.1μl后,对照组大鼠的平均动脉压（MAP）升高,RVLM内Ach含量增多,而应激性高血压组大鼠MAP的变化显著小于对照组。结论：应激性高血压大鼠PAG内NOS阳性神经元发生的可塑性变化,可能经RVLM内Ach介导,参与了该病的形成。     

吗啡耐受和电针耐受时大鼠脑内血管紧张素原的基因表达加速

我们以往的工作表明,脑内血管紧张素Ⅱ(AⅡ)作为一种抗阿片物质参与吗啡耐受和电针耐受。本工作探讨在此过程中脑内AⅡ的基因表达是否加速。采用酚抽提法提取大鼠脑组织总RNA,使用人工合成的寡脱氧核糖核酸探针进行打点杂交。放射自显影结果表明,多次皮下注射吗啡或连续数小时电针的大鼠脑血管紧张素原(Ang)mRNA含量明显升高。在IBAS图象分析仪上,测量各杂交点自显影曝光斑的积分光密度值(I.O.D.)表明,连续注射吗啡1d或4d使Ang mRNA分别增高1倍或8倍;电针3或6h使Ang mRNA分别增高5倍或13倍。说明大鼠经3—4h吗啡或电针处理,即可引起在转录水平上脑内Ang基因表达加强。     

应激引起血压升高大鼠血管 升压素V1受体mRNA水平改变

实验在雄性Sprague-Dawley大鼠上进行。 实验动物被随机分为对照组和应激组, 应激组大鼠每天给予电击足底结合噪声的应激刺激, 每日2次, 每次2 h。 应激组大鼠在接受连续15 d的慢性应激刺激后, 其尾动脉收缩压与对照动物相比有显著升高。 对照组为16.25±0.63 kPa (n=7); 应激组为19.55±1.45 kPa (n=8, P<0.05)。 用RT-PCR结合Southern印迹核酸分子杂交技术观察到, 血管升压素(vasopressin, AVP)V     

贯叶连翘对应激大鼠生长和脑单胺类神经递质含量的影响

为探讨贯叶连翘对慢性应激大鼠生长和脑单胺类神经递质的影响,用15只大鼠设置对照组、应激组和贯叶连翘组3组实验。应激组和贯叶连翘组均进行7天的应激刺激后,贯叶连翘组灌胃贯叶连翘10d。实验结束后,取3组大鼠的脑组织,用高效液相色谱法测定高香草酸(HVA)、去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的含量。结果表明,应激组大鼠日增重明显低于对照组;而贯叶连翘组大鼠的日增重明显高于应激组。应激组大鼠海马、纹状体和前额叶中的HVA、NE、DA和5-HT与对照组间均无显著差异。贯叶连翘组大鼠纹状体中的DA含量明显高于应激组;而前额叶中的DA则明显低于应激组。因此,贯叶连翘对慢性应激引起的大鼠生长受抑有缓解作用,对其脑内单胺类神经递质有部分调节作用。     

侧脑室注射血管紧张素Ⅱ对大鼠血压和缰核内神经元电活动的影响

实验观察了侧脑室注射（ｉｃｖ）及缰核（ｈａｂｅｎｕｌａ ｎｕｃｌｅｕｓ）内微电泳血管紧张素Ⅱ（ＡⅡ）与「Ｓａｒ＾１,Ｔｈｒ＾３」－ＡⅡ（ＳＴ－ＡⅡ,ＡⅡ拮抗剂）对正常和诮激性高血压（ｓｔｒｅｓｓ－ｉｎｄｕｃｅｄ ｈｙｐｅｒｔｅｎｓｉｏｎ ＳＩＨ）大鼠血压及内外侧缰核（ＭＨｂ、ＬＨｂ）内心血管神经元入电活动的影响。结果如下：ｉｃｖ ＡⅡ或ＳＴ－ＡⅡ,正常鼠和ＳＩＨ大鼠血压均升高或降低,ＳＩＨ鼠较正常     

缰核参与应激性高血压的形成及其机制研究

电击大鼠足底形成应激性高血压（ＳＩＨ）,研究了缰核（Ｈｂ）在其中的作用机制。损毁Ｈｂ可降低ＳＩＨ升高的幅度。ＳＩＨ鼠内外侧Ｈｂ（ＭＨｂ,ＬＨｂ）对谷氨酸（Ｇｌｕ）的敏感性高于正常鼠。足底电击使血浆和Ｈｂ内血管紧张素Ⅱ（ＡｎｇⅡ）明显升高,侧脑室和ＭＨｂ分别注射ＡｎｇⅡ或ｓａｒａｌａｓｉｎ,在ＳＩＨ鼠引起明显的血压变化。微电泳ＡｎｇⅡ,ｓａｒａｌａｓｉｎ可分别明显改变ＳＩＨ鼠Ｈｂ内神经元的放电活动。     

Prolonged expression of c-Fos protein in the lateral habenular nucleus of the Japanese monkey (Macaca fuscata) after eye enucleation

To elucidate the effect of traumatic stress on the lateral habenular nucleus, we investigated the time course of the expression of c-Fos protein in this nucleus of the Japanese monkey (Macaca fuscata) after enucleation of one eye using c-Fos protein immunocytochemistry. c-Fos protein-like immunoreactive neurons were significantly increased; the increase started 1 h after the enucleation and remained high for 3-9 h in the lateral habenular nucleus on both sides. These results suggest that the prolonged expression of c-Fos protein occurred in the lateral habenular nucleus after traumatic stress through multiple transsynaptic activations.     

川芎嗪抑制血管紧张素Ⅱ诱导的平滑肌细胞NF-κB激活和骨形成蛋白-2表达降低

本文旨在观察血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）对血管平滑肌细胞核转录因子-κB（nuclear factor-κB,NF-κB）的活性及骨形成蛋白-2（bone morphogenetic protein-2,BMP-2）表达的影响,以探讨AngⅡ参与动脉粥样硬化的机制,并探讨川芎嗪是否能抑制AngⅡ的促动脉粥样硬化作用。采用Western blot、免疫组化和原位杂交等方法分别检测AngⅡ刺激和川芎嗪干预后NF-κB活性、BMP-2蛋白和mRNA表达的变化。结果显示：（1）AngⅡ刺激激活NF-κB。AngⅡ刺激15min即有NF-κB p65核转移,30min达高峰（P〈0．01）,1h后减退。川芎嗪抑制AngⅡ诱导的NF-κB激活,与AngⅡ组比较,川芎嗪＋AngⅡ组NF-κB活性显著降低（P〈0．01）。（2）AngⅡ刺激6h时BMP-2表达增强（P〈0．05）,12h时减弱（P〈0．01）,24h时更弱（P〈0．01）。川芎嗪＋AngⅡ组中,川芎嗪干预6h时BMP-2表达亦增强,12与24h时保持正常水平。（3）川芎嗪对正常细胞的NF-κB活性和BMP-2表达无影响。以上结果表明,AngⅡ刺激后激活NF-κB并最终使生长抑制因子BMP-2表达下降,这可能是其参与动脉粥样硬化发生的机制之一。BMP-2一过性增高可能不依赖NF-κB通路的激活。川芎嗪可抑制AngⅡ诱导的NF-κB激活与BMP-2表达降低,提示它在抗动脉粥样硬化形成中起重要作用。     

The Effects of Angiotensin II and Angiotensin-(1–7) in the Rostral Ventrolateral Medulla of Rats on Stress-Induced Hypertension

We have shown that angiotensin II (Ang II) and angiotensin-(1–7) [Ang-(1–7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1–7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1–7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and γ-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT₁ receptor (AT₁R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT₂ receptor (AT₂R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1–7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT₁R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT₂R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT₁R, not Ang-(1–7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release.     

辣椒素引起脑干内心血管活动相关核团中c-fos的表达

在１６只切断两侧缓冲神经的大鼠,观察颈总动脉注射辣椒素对脑干内心血管活动相关核团ｃ－ｆｏｓ原癌基因表达的影响。在剂对照组大鼠脑干,仅见少数Ｆｏｓ蛋白样免疫反应（ＦＬＩ）神经元。与对照组相比,颈总动脉注射辣椒素（１０μｍｏｌ,０．１ｍｌ）时,脑干内巨细胞旁外侧核（ＰＧＬ）、蓝斑（ＬＣ）、最后区（ＡＰ）和孤束核（ＮＴＳ）等部位的ＦＬＩ神经元显著增加,而中脑中央灰质（ＰＡＧ）和中缝核群（ＲＮ）的ＦＬＩ神     

Effects of angiotensin II on the spontaneous activity of rostral ventrolateral medullary cardiovascular neurons and blood pressure in spontaneously hypertensive rats

The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesthetized spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar Kyoto rat (WKY). It was found that Ang II elicited dose-dependent excitatory responses in a subpopulation of RVL cardiovascular neurons, followed by a subsequent increase in blood pressure. These effects of Ang II were significantly greater in SHR than in WKY. The effects were attenuated or abolished by co-administration of Ang II antagonist, [Sar¹, Ile⁸]-Ang II. Pre-administration of [Sar¹, Ile⁸]-Ang II to RVL using bilateral microinjection attenuated the blood pressure effects of intracerebroventricularly administered Ang II by as much as 70%. These results indicated that spinal projecting RVL cardiovascular neurons are important in mediating the pressor action of Ang II. The enhanced sensitivity and responsiveness of RVL cardiovascular neurons to Ang II may be pertinent to the genesis of hypertension in adult SHR.     

Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.