通脉颗粒对自发性高血压大鼠血管重塑的影响

高血压病是临床常见病、多发病，高血压血管重构是指高血压状态下血管结构和功能的改变。目前考虑其形成机制为血液动力学的刺激、血管活性物质的作用及外基质的调节等引起血管平滑肌细胞（VSMC）的增殖、凋亡与重塑。故对高血压病的治疗并不能仅仅局限于降压，还应着眼于逆转高血压血管重构（VR）。通脉颗粒（TM）是临床治疗高血压病的验方。     

益肾法对自发性高血压大鼠肾保护作用的研究

目的:观察益肾法对自发性高血压大鼠(SHR)肾保护作用。方法:将60只SHR随机分为模型对照组、杞菊地黄丸组、二仙汤组、杞菊地黄丸与二仙汤合方组、合方小剂量组和苯那普利组。分别观测血压动态变化情况和肾血流情况。结果:苯那普利组、杞菊地黄丸组、杞菊地黄丸与二仙汤合方组和合方小剂量组的收缩压均有显著性降低(P<0.05),其中前3组的收缩压降低得更为明显(P<0.01)。各治疗组的肾血流高于模型对照组(P<0.01)。结论:杞菊地黄丸、杞菊地黄丸与二仙汤合方均可以降低SHR血压。杞菊地黄丸、二仙汤和杞菊地黄丸与二仙汤合方均可以提高SHR的肾血流量。     

益肾法对自发性高血压大鼠血压和肾血流影响的研究

目的:观察益肾法对自发性高血压大鼠(SHR)血压和肾脏血流的影响。方法:将16只SHR随机分为模型对照组,杞菊地黄丸组,二仙汤组和苯那普利组,连续灌胃给药6周。分别观测血压动态变化和肾血流情况。结果:滋阴补肾的杞菊地黄丸组和苯那普利组的收缩压低于模型对照组(P<0.05),其降血压作用强于温补肾阳的二仙汤;二仙汤组肾血流高于模型对照组(P<0.05),其对肾血流的改善作用强于杞菊地黄丸。结论:益肾中药可以降低SHR的收缩压,以滋阴补肾的杞菊地黄丸的降压作用更为显著。益肾中药可以改善SHR的肾血流量,以温补肾阳的二仙汤的作用更为显著。     

软脉灵抑制自发性高血压大鼠血管重塑的实验研究

目的观察软脉灵对自发性高血压大鼠（SHR）血管重塑的影响。方法12周龄雄性SHR36只，随机分为4组,空白组、软脉灵大剂量和小剂量组、阳性对照组。血压正常的WKY为正常对照组。治疗前及治疗12周后测动脉血压（SBP），取胸主动脉及肠系膜三级动脉，HE染色，计算血管管壁面积／管腔面积（W／L）及管壁厚度／管腔半径（Tw／R1）。结果软脉灵大剂量和小刹量组治疗12周后，两组SBP均显著低于SHR（P〈0．01）。与SHR相比，软脉灵大剂量组治疗12周后，胸主动脉W／L及Tw／R1均明显降低（P〈0．05或P〈0．01）；且RH与LOS相比无统计学意义，而软脉灵小剂量组与SHR相比差异无统计学意义。与SHR相比，软脉灵大剂量和小剂量组治疗12周后，肠系膜三级动脉W／L均显著降低（P〈0．05）。给予软脉灵大剂量治疗后，Tw／R1明显降低（P〈0．05），而软脉灵小剂量组对Tw／R1没有影响。结论软脉灵可抑制SHR血压的发展，减轻胸主动脉及肠系膜三级动脉的重塑。     

天麻舒心方对自发性高血压大鼠阻力血管富营养重塑的干预效果

目的从显微形态及超微结构层面探讨天麻舒心方对自发性高血压大鼠(SHR)阻力血管富营养重塑的干预效果。方法中药高、中、低剂量组,阳性对照组(对照组),模型对照组(模型组),各10只SHR;10只Wistar大鼠作为正常对照组(空白组),各给药组分别给予相应剂量的天麻舒心浸膏液、氯沙坦钾混悬液,模型组及空白组予以相同体积的蒸馏水。18周后,处死动物并留取肠系膜三级动脉标本;倒置相差显微镜观察血管显微形态,测定并计算管腔外直径、管腔内直径、中膜厚度、中膜横断面面积、中膜厚度/管腔内半径;透射电子显微镜观察肠系膜三级动脉超微结构。结果与空白组比较,模型组中膜横断面面积未见改变,差异无统计学意义(P0.05);管腔外直径、管腔内直径减少,差异有统计学意义(P0.05,P0.01);中膜厚度、中膜厚度/内腔半径增加,差异有统计学意义(P0.01),内弹力层不连续,中膜SMC变形、胶原纤维增生。与模型组比较,对照组和中药各剂量组管腔内直径均增加,差异有统计学意义(P0.05,P0.01);中膜厚度、中膜厚度/内半径均减少,差异亦有统计学意义(P0.05,P0.01),内弹力层、中膜平滑肌细胞变形及胶原纤维增生得到不同程度改善。结论 SHR阻力血管出现富营养重塑,天麻舒心方可以从显微形态及超微结构等层面改善高血压阻力血管富营养重塑。     

降压益肾颗粒对自发性高血压大鼠降压疗效观察

目的:观察降压益肾颗粒对自发性高血压大鼠降压疗效。方法:采用尾容积法测清醒大鼠间接血压及颈动脉插管测颈动脉内直接血压。结果:急性降压实验时,尼群地平对照组及降压益肾治疗组血压均有下降,2小时时尼群地平组降压达高峰,降压益肾大剂量组和小剂量组峰值在4小时时出现,治疗期间大剂量组和小剂量组降压疗效与尼群地平组比较无显著差异。结论:降压益肾颗粒具有确切的降压疗效,而且作用持久。     

降压益肾颗粒对自发性高血压大鼠胰岛素抵抗的影响

目的:观察中药复方降压益肾颗粒对自发性高血压大鼠(SHR)胰岛素抵抗(IR)的影响.方法:将SHR 32只分为降压益肾大、小剂量组,尼群地平组,模型组各8只,治疗8周后处死,以葡萄糖氧化酶法、放射免疫双抗体法测定血清血糖(G)及胰岛素(I)含量.结果:治疗后降压益肾颗粒大、小剂量组G和I均明显降低,优于对照组(P＜0.01～0.05),且呈剂量相关性.结论:降压益肾颗粒剂对高血压病IR具有确切的改善作用.     

降压益肾颗粒对自发性高血压大鼠血及肾脏局部ET的影响

1材料与方法1·1实验动物与分组自发性高血压大鼠(SHR)32只12周龄,体重(165±21·9)g,雌雄各半。由上海市高血压病研究所提供,合格证号:0237-1。编号后随机分为4组,即降压益肾颗粒大、小剂量组、尼群地平组、生理盐水组,每组均为8只。大、小剂量组分别以相当于成人每天口服剂量的5倍量和2倍量即8·5g生药/kg·d-1、3·4g生药/kg·d-1二种浓度的降压益肾颗粒混悬液灌胃,尼群地平混悬液4·53g/kg·d-1,相当于成人常规剂量的2倍量浓度灌胃,体积均为2ml,每天1次,模型组每天1次灌服同体积的生理盐水,共灌胃8周。1·2药品与试剂降压益肾颗粒(由…     

通脉宁颗粒对自发性高血压大鼠血压及血管重构的影响

目的 :通过观察通脉宁颗粒 (TMN)对自发性高血压大鼠 (SHR)血压及胸主动脉血管重构的影响 ,为该药临床推广提供实验依据。方法 :以SHR为模型 ,采用无创性套尾法测定尾动脉收缩压 ,观察TMN对SHR血压的影响 ,并结合电镜及图象分析观察TMN对SHR胸主动脉血管重构的影响。结果 :TMN对SHR有降低血压、逆转胸主动脉血管重构的作用。     

复方丹参滴丸对自发性高血压大鼠血管重构的影响

目的探讨复方丹参滴丸（DSP）对自发性高血压大鼠（SHR）血管重构的影响。方法将32只8周龄雄性SHR随机分为4组,DSP小剂量组、DSP大剂量组、福辛普利组、SHRc组。另选8周龄雄性Wistar大鼠为正常对照组。5组分别用灌胃法给药或给蒸馏水8周,测定大鼠尾动脉收缩压、胸主动脉与肠系膜动脉中层壁厚（M）、管腔内径（L）及二者的比值（M／L）。结果与Wistar组比,SHRc组主动脉中层壁[Wistar组：（85±10）μm比SHRc组（120±7）μm]与肠系膜动脉中层壁[Wistar组：（61±8）μm比SHR模型组（84±8）μm]显著增厚（P〈0．05）,中层壁厚与管腔内径比值（M／L）也显著增大（P〈0．05）;与SHRc组比,DSP大剂量组[肠系膜动脉M：（65±5）μm;主动脉M：（94±7）μm]、小剂量组[肠系膜动脉M：（70±3）μm;主动脉M：（97±9）μm]与福辛普利组[肠系膜动脉M：（64±7）μm;主动脉M：（93±6）μm]SHR主动脉与肠系膜动脉的M及M／L均明显减轻（P〈0．05）,而各治疗组间无统计学意义（P〉0．05）。结论复方丹参滴丸可抑制SHR的血管壁重构。     

Effect of the flavonoid fraction of Lithocarpus polystachyus Rehd. on spontaneously hypertensive and normotensive rats

Ethnopharmacological relevance

Lilhocarpus polystachys Rehd. (Sweet Tea, ST) is a folk herbal medicine that has been traditionally used as a natural remedy for hypertension in China, whose mechanism remains unveiled. Flavonoid fraction is considered as the major active components in ST. This study aimed to provide experimental evidence for the anti-hypertension activity of flavonoid fraction of ST (ST-F) and investigate the underlying mechanism. The effect of ST-F on the blood pressure of normotensive rats was also to be determined.

Materials and methods

Spontaneously hypertensive rats (SHRs) were treated with ST-F daily for 10 weeks. Blood pressure of SHRs was measured before and biweekly during ST-F treatment. Subsequently, animals were sacrificed either immediately at the end of treatment or 2 weeks after ST-F treatment discontinuance. The activities of plasma rennin (PRA), angiotensin II (Ang-I), endothelin (ET), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as well as skin microcirculatory flux. In normotensive rats, blood pressure was determined after six months' treatment of ST-F.

Results

ST-F treatment significantly reduced the blood pressure of SHRs along with decreasing plasma levels of PRA and Ang II. ST-F did not show obvious effects on plasma levels of ET, NO or SOD, but it significantly decreased the plasma level of MDA and improved skin microcirculatory flux. Compared to the anti-hypertensive drug enalapril, ST-F showed a modest effect on lowering blood pressure of SHRs without obvious withdrawal reactions. But long-term intake of ST-F did not change the blood pressure in normotensive rats.

Conclusion

ST-F had an antihypertensive effect on SHRs. The underlying mechanism could be related to modulation on the rennin–angiotensin–aldosterone system (RAAS) and antioxidation system, as well as regulation of skin microcirculation. Compared to its anti-hypertensive effect on SHRs, ST-F did not cause hypotension in normotensive rats. The results indicated that ST-F could potentially be used as natural drugs or functional foods for preventing hypertension.     

镇肝熄风汤对自发性高血压大鼠血管重塑的影响

目的观察镇肝熄风汤对自发性高血压大鼠(SHR)血管组织形态学改变及血管平滑肌细胞增殖核抗原(PCNA)的表达,探讨镇肝熄风汤对血管重塑的影响。方法将24只14周龄的雄性SHR随机分为SHR组、镇肝熄风汤组、依那普利组,每组各8只,同时以同源雄性京都威斯特大鼠(WKY)8只作为对照组,镇肝熄风汤组灌服镇肝熄风汤15g/(kg.d),依那普利组灌服依那普利0.01g/(kg.d),SHR组及WKY组每日灌服等容积的0.9%氯化钠注射液,每日灌胃2次。灌胃给药8周后,采用苏木色精-伊红(HE)染色法观察胸主动脉病理改变,免疫组化法检测主动脉血管平滑肌细胞PCNA的表达。结果与WKY组相比,SHR组胸主动脉中膜增厚,PCNA表达增强,镇肝熄风汤组和依那普利组可有效抑制PCNA表达增强,改善动脉中膜厚度。结论镇肝熄风汤可能通过抑制血管平滑肌细胞增殖,改善血管重塑。     

钩藤碱对自发性高血压大鼠的降压作用及其对血管的调节机制探讨

目的研究钩藤碱连续给药后对自发性高血压大鼠(SHR)收缩压(SBP)的影响及其对血管的调节机制。方法取雄性SHR,随机分为模型组(等容量蒸馏水),卡托普利阳性对照组(6.25 mg/kg),钩藤碱低、中、高剂量(1.25、2.50、5.00 mg/kg)组,另取SD雄性大鼠作为对照组(等容量蒸馏水),各给药组连续ig给药21 d,测定给药前和给药第7、14、21天的大鼠尾动脉SBP,末次给药后采血,检测血浆血管紧张素II(Ang II)、非对称二甲基精氨酸(ADMA)、血管紧张素II 1型受体(AT1R)和血清NO、一氧化氮合酶(NOS)水平。结果与模型组比较,钩藤碱各剂量组可显著降低SHR的SBP值;模型组大鼠血浆Ang II、ADMA、AT1R水平显著升高,且血清中NO和NOS水平显著下降,而钩藤碱能够逆转上述指标的改变(P<0.05、0.01)。结论钩藤碱对SHR有显著降低SBP作用,能降低血浆Ang II、ADMA水平,升高血清NO和NOS水平,有保护血管内皮功能的作用。     

Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodelingOA

Objective: To investigate the bioactive components of Sangqi Qingxuan formula(SQQX), predict the pharmacological targets, and explore the mechanism of hypertensive vascular remodeling(HVR).Methods: Network pharmacology was adopted to predict how SQQX acts in HVR. The effectiveness was assessed by blood pressure measurements and pathological morphology observation based on a spontaneously hypertensive rat model, while the mechanism of SQQX on HVR was validated by immunohistochemistry(IHC) and wes...     

Effects of onion and garlic extracts on spontaneously hypertensive rats

The effects of ethanolic extracts of onion and garlic, on blood pressure and plasma fatty acid composition were studied in spontaneously hypertensive rats. Oral administration of the extracts for up to 7 weeks during a normal salt diet or during a high salt diet did not influence the blood pressure. The percentage of two fatty acids in platelet-rich plasma changed following garlic supplementation. The increase in the relative amount of linoleic acid and the simultaneous decrease in arachidonic acid were statistically significant. In the case of onion only the decrease in arachidonic acid was statistically significant. The changes in lipid metabolism could be responsible for the apparent beneficial effects of onion and garlic on the inhibition of platelet aggregation.     

盐酸乌拉地尔滴鼻剂对自发性高血压大鼠血压的影响

目的观察自制盐酸乌拉地尔滴鼻剂对自发性高血压大鼠(SHR)的降压作用。方法将自发性高血压大鼠9只SHR在清醒状态下随机分成3组,实验组3只在清醒状态下予盐酸乌拉地尔滴鼻剂滴鼻给药,阳性对照组予盐酸乌拉地尔注射剂尾静脉注射给药,阴性对照组予生理盐水滴鼻。给药后即测尾动脉血压。结果实验组和阳性对照组降压作用与生理盐水组比较均有显著性差异(P<0.05)。结论自制盐酸乌拉地尔滴鼻剂能够使自发性高血压大鼠血压迅速降低。     

复元醒脑汤对高血压性脑出血大鼠血-脑屏障通透性的干预作用

目的探讨复元醒脑汤对高血压性脑出血大鼠脑水肿及血－脑屏障通透性的干预作用。方法将SHR大鼠随机分为四组,分别为假手术组、模型组、安宫牛黄胶囊组、复元醒脑汤组,并与WKY大鼠假手术组对照。每组20只大鼠。模型组、安宫牛黄胶囊组和复元醒脑汤组在收缩压达到21．3KPa基础上以胶原酶加肝素尾状核注射法诱发脑出血,建立高血压性脑出血模型,其中安宫牛黄胶囊组和复元醒脑汤组分别给予相应药物干预,于造模后连续灌胃3天。两假手术组脑内注射及灌胃均为生理盐水,模型组灌胃为生理盐水。观测各组动物神经缺损行为体征、脑组织含水量、血．脑屏障通透性变化。结果SHR模型组与WKY假手术组、SHR假手术组比较,神经缺损行为体征评分升高（均P〈0．01）;脑组织含水量增加（均P〈0．01）,脑组织中伊文思蓝含量亦增加（均P〈0．01）;SHR复元醒脑汤和SHR安宫牛黄胶囊两治疗组分别与SHR模型组比较,神经缺损行为体征评分降低（均P〈0．01）,脑组织含水量减少（均P〈0．01）,脑组织中伊文思蓝含量亦降低（均P〈0．01）;上述指标变化复元醒脑汤组与安宫牛黄胶囊组比较差异无统计学意义（均P〉0．05）。结论复元醒脑汤可降低血-脑屏障通透性,减轻脑水肿程度,改善神经功能缺损．达到治疗高血压性脑出血的目的。     

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

Ethnopharmacological relevance

Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family Alliaceae, most commonly associated with onions and garlic. In South Africa, this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of Tulbaghia violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats; and to find out the mechanism(s) by which it acts.

Materials and methods

The MLE of Tulbaghia violacea (5–150 mg/kg), angiotensin I human acetate salt hydrate (ang I, 3.1–100 μg/kg), angiotensin II human (ang II, 3.1–50 μg/kg), phenylephrine hydrochloride (phenylephrine, 0.01–0.16 mg/kg) and dobutamine hydrochloride (dobutamine, 0.2–10.0 μg/kg) were infused intravenously, while the BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab.

Results

Tulbaghia violacea significantly (p < 0.01) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. Ang I, ang II, phenylephrine and dobutamine all increased the BP dose-dependently. The hypertensive effect of ang I and the HR-increasing effect of dobutamine were significantly (p < 0.01) decreased by their co-infusion with Tulbaghia violacea (60 mg/kg). However, the co-infusion of ang II or phenylephrine with Tulbaghia violacea (60 mg/kg) did not produce any significant change in BP or HR when compared to the infusion of either agent alone in the same animal.

Conclusions

Tulbaghia violacea reduced BP and HR in the SHR. The reduction in BP may be due to actions of the MLE on the ang I converting enzyme (ACE) and β₁ adrenoceptors.     

白蒺藜有效组分对自发性高血压大鼠心肌结缔组织生长因子表达的影响

目的观察白蒺藜有效组分对自发性高血压大鼠心肌结缔组织生长因子（CTGF）表达的影响,探讨白蒺藜有效组分改善心室重构的可能作用机制。方法 32只14周龄雄性自发性高血压大鼠随机分为模型组、卡托普利组、白蒺藜组、联用组,每组8只,同周龄雄性Wistar大鼠8只作为正常对照组。用药组分别给予卡托普利30mg.kg-1.d-1,白蒺藜有效组分15mg.kg-1.d-1,白蒺藜有效组分15mg.kg-1.d-1＋卡托普利30mg.kg-1.d-1,模型组及对照组采用等量0.9%NaCl溶液,连续灌胃8周。采用尾动脉容积法测定血压;分离左心室,透射电镜观察心肌超微结构;RT-PCR法检测心肌转化生长因子β1（TGFβ1）、CTGF mRNA含量变化。结果与Wistar大鼠比较,14周龄SHR大鼠收缩压明显升高（P〈0.01）。8周后,模型组大鼠收缩压明显较14周龄时明显升高（P〈0.05）,通过透射电镜对心肌超微结构观察提示,22周龄SHR出现明显的心肌纤维化;且模型组TGFβ1及CTGF mRNA较正常组表达明显增加（P〈0.05）。与模型组比较,白蒺藜组收缩压明显下降（P〈0.01）,并可明显改善心肌超微结构,显著下调TGFβ1及CTGF mRNA水平（P〈0.05）。卡托普利和白蒺藜联用可明显下调TGFβ1mRNA水平（P〈0.05）。结论自发性高血压大鼠心室肌TGFβ1及CTGF表达明显增加,白蒺藜有效组分可显著抑制TGFβ1及CTGF基因表达水平,从而保护高血压病所致的靶器官损伤。     

芩丹胶囊对老年自发性高血压大鼠血管外膜重构作用机制的研究

目的观察芩丹胶囊（QD）的降压效果以及对胸主动脉外膜ADM、TGF-β1和Ⅰ、Ⅲ胶原的作用,探讨QD改善高血压血管外膜重构的作用机制。方法将老年自发性高血压大鼠（SHR）随机分为模型组（SHR组）、QD大剂量组（SHR＋QDH组）、QD小剂量组（SHR＋QDL组）、氯沙坦组（SHR＋Los组）,另设老年Wistar-Kyoto（WKY）大鼠空白对照组（WKY组）及正常用药组（WKY＋QDH组）。给药组分别灌胃给予相应药物,SHR组和WKY组灌胃给予等量0.9%NaCl溶液。测量各组大鼠收缩压;免疫组化法观察ADM和TGF-β1在胸主动脉外膜的蛋白表达;以间接免疫荧光组织化学染色配合激光共聚焦显微镜扫描,对胸主动脉外膜Ⅰ、Ⅲ胶原的表达进行荧光定量分析。结果与SHR组比较,SHR＋QDH组、SHR＋QDL组和SHR＋Los组收缩压均下降（P〈0.05）;ADM、TGF-β1和Ⅰ、Ⅲ胶原蛋白表达均降低（P〈0.05）。SHR＋QDH组比SHR＋QDL组效果更好（P〈0.05）。与WKY组比较,SHR组、SHR＋QDH组、SHR＋QDL组、SHR＋Los组收缩压均升高（P〈0.05）,ADM、TGF-β1和Ⅰ、Ⅲ胶原蛋白表达均增多（P〈0.05）,而WKY＋QDH组各项指标差异无统计学意义（P（0.05）。结论 QD不仅能够有效降低SHR血压,而且能够下调TGF-β1和Ⅰ、Ⅲ胶原表达,抑制外膜胶原合成,具有拮抗作用的ADM也随之下降,从而改善和逆转血管外膜重构。