葶苈子水提液对动物实验性心室重构的影响

目的研究葶苈子水提液对异丙肾上腺素(ISO)诱发小鼠,L-甲状腺素(L-Thy)诱发大鼠实验性心室重构的影响。方法小鼠每天scISO2mg/kg,连续7d;大鼠每天ipL-Thy0.3mg/kg,连续10d,制备心室重构动物模型。各组小鼠每天ig葶苈子水提液6、12g/kg和美托洛尔0.06g/kg,连续7d后,检测心脏指数、血浆环磷酸腺苷(cAMP)、心肌血管紧张素(Ang)量的变化;各组大鼠每天ig葶苈子水提液4、8g/kg和卡托普利0.02g/kg10d后,检测心脏指数、血浆中醛固酮(ALD)及左心肌Ang、羟脯氨酸(Hyp)量的变化。结果模型小鼠的心脏指数、cAMP、Ang量均明显升高,给予美托洛尔0.06g/kg或葶苈子水提液12g/kg均可抑制小鼠左心室重构和肥厚,降低心脏指数和血清cAMP水平及心肌Ang的量(P<0.05)。模型大鼠也出现心肌纤维化,心脏指数、心肌Ang、血浆ALD、心肌Hyp量均明显升高,给予卡托普利0.02g/kg或葶苈子水提液4、8g/kg均可降低大鼠心脏指数和Ang、ALD及心肌Hyp水平(P<0.05)。结论葶苈子水提液具有抑制实验动物心肌肥大、心室重构的作用,其作用机制可能与抑制交感神经系统兴奋性及抑制Ang、ALD等神经内分泌因子激活有关。     

雷米普利对压力超负荷性心肌肥厚大鼠的影响

目的：观察雷米普利对心肌肥厚大鼠的影响。方法：结扎Wistar雄性大鼠腹主动脉建立压力超负荷性心肌肥厚大鼠模型,用雷米普利（5mg／kg）对心肌肥厚大鼠进行研究,给药8周后用放免法测定血液中AngⅡ和ET含量,同时设立Wistar雄性大鼠假手术组和心肌肥厚不给药组。结果表明：雷米普利可降低心肌肥厚组大鼠血液中AngⅡ和ET的含量。结论：雷米普利能够抑制大鼠心肌肥厚。     

血管紧张素Ⅱ在左心室肥厚发病机制中的作用

新近研究发现,左心室肥厚可见于高血压的极早期,甚至少数高血压患者在血压升高前就存在室壁肥厚.这些资料表明左心室肥厚可由独立于血压之外的因素导致.越来越多的证据表明,左心室肥厚和神经体液内分泌因素密切相关.左心室肥厚作为心肌对心肌损伤及心脏超负荷的一种反应,反映了体内生长促进因子[如血管紧张素Ⅱ(AngⅡ)、细胞因子、生长因子、去甲肾上腺素、甲状腺素等]和生长抑制因子(如心钠素、缓激肽、前列腺素及NO等)之间效应的失衡.前者直接调节和促进心肌细胞生长,后者则可扩张血管、减轻心脏负荷、增加胶元降解,对抗AngⅡ等生长促进因子的作用.本文综述AngⅡ在左心室肥厚发病机制中的作用.     

丝氨酸通过甘氨酸受体缓解血管紧张素Ⅱ诱导的心肌纤维化

目的：探索丝氨酸是否对心肌纤维化具有保护作用及其可能的机制。方法：通过微渗透泵持续给予血管紧张素Ⅱ（angiotensin Ⅱ,Ang Ⅱ）28 d建立小鼠心肌纤维化模型,观察丝氨酸对小鼠心肌纤维化的效应。乳大鼠原代心脏成纤维细胞单独培养或与原代心肌细胞共培养,分别用Ang Ⅱ和丝氨酸处理,检测心脏成纤维细胞胶原Ⅰ和胶原Ⅲ的表达;并检测丝氨酸对Ang Ⅱ诱导的原代心肌细胞炎症因子表达有无影响。应用siRNA技术干扰心肌细胞甘氨酸受体（glycine receptor, GlyR）,并检测丝氨酸抑制心肌纤维化是否依赖GlyR。结果：Masson染色提示,预防性使用丝氨酸可以减轻小鼠心肌纤维化;定量PCR结果提示丝氨酸可以抑制受损心脏组织中胶原Ⅰ和Ⅲ增多。虽然丝氨酸能直接抑制受损心肌细胞转化生长因子β和内皮素-1释放,但它并不能直接抑制心脏成纤维细胞合成胶原增多,只有与心肌细胞共培养时,丝氨酸才能抑制心脏成纤维细胞的胶原Ⅰ和Ⅲ产生增多。此外,当心肌细胞的GlyR表达降低后,丝氨酸抑制胶原生成的保护效应随之消失。结论：丝氨酸可通过激活心肌细胞甘氨酸受体,减少心肌细胞炎症反应,间接抑制心脏成纤维细胞产生胶原,进而改善心肌纤维化。     

牛磺酸对高血压大鼠心肌肥厚、心肌细胞凋亡、NO及血管紧张素Ⅱ含量的影响

目的探讨牛磺酸对肾血管性高血压大鼠心肌肥厚、心肌细胞凋亡、一氧化氮（NO）及血管紧张素Ⅱ（Ang Ⅱ）含量的影响。方法采用两肾一夹（2K1C）型肾血管性高血压大鼠模型。所有大鼠被随机分为3组（每组20只）：假手术对照组、高血压对照组、牛磺酸治疗组。于术后第5周开始给予牛磺酸50mg·kg^-1·d^-1。采用标准尾套法间接检测清醒大鼠血压。给药8周后,大鼠处死,分离其左室心肌以用于检测左室质量/体质量比、心肌细胞凋亡指数（AI）、NO和Ang Ⅱ含量。结果与假手术组大鼠相比,未给药2K1C高血压大鼠血压明显升高,左室质量体质量比、心肌AI和Ang Ⅱ含量均升高,心肌NO含量降低。应用牛磺酸治疗则明显降低了肾动脉狭窄术后大鼠的血压、左室质量/体质量比、心肌Ai和Ang Ⅱ含量;同时也升高了2K1C高血压大鼠心肌NO含量。结论长疗程牛磺酸治疗可抑制高血压大鼠心肌肥厚和心肌细胞凋亡发生,其作用机制与药物调控心源性活性物质分泌水平有关。     

环孢素A对血管紧张素Ⅱ诱导的新生大鼠心肌细胞肥大及c-fos表达的影响

目的 在培养的新生大鼠心肌细胞上观察环孢素A(CsA)对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大和c-fos表达增加的作用，借以探讨CsA抑制血管紧张素Ⅱ诱导心肌肥厚的机制。方法 用Bradford比色法测量心肌细胞总蛋白的含量；用Western Blot方法定量测定心肌细胞c-fos蛋白含量。结果 ①AngⅡ可明显增加心肌细胞的蛋白总量，CsA可以浓度依赖地抑制AngⅡ诱导的心肌蛋白含量的增加；②AngⅡ可诱导rfos蛋白表达增加，CsA可浓度依赖性抑制AngⅡ的这一作用。结论 CsA可以抑制AngⅡ诱导的培养新生大鼠心肌细胞肥大，抑制AngⅡ引起的心肌细胞c-fos蛋白表达增加可能是其作用机制之一。     

玄参水提物对心室重构大鼠心肌纤维化的影响

目的探讨玄参对心室重构大鼠心肌纤维化的影响及其作用机制。方法腹主动脉缩窄法制备大鼠心室重构模型。8周药物干预后,测定大鼠左室及全心肥厚指数(LVWI、HWI);紫外分光光度法测心肌羟脯氨酸的量(hydroxproline,Hyp);病理切片HE染色观察心肌细胞横断面面积;RT-PCR测定心肌组织转化生成因子β1基因(TGF-β1mRNA)表达水平。结果玄参水提液能降低心肌肥厚指数、羟脯氨酸量,减小左心室心肌细胞的横断面面积;显著降低TGF-β1mRNA表达水平。结论玄参水提液对心肌细胞和间质胶原重构两方面都有显著的抑制作用,抗心室重构的作用机制与抑制TGF-β1mRNA表达有关。     

地高辛通过上调RGS2表达以减缓AngⅡ诱导小鼠高血压性心肌肥厚发生发展的研究

目的：通过观察地高辛（Digoxin）干预血管紧张素Ⅱ（AngⅡ）诱导的ApoE‐/‐小鼠高血压性心肌肥厚模型后,对G蛋白调节因子2（regulator of G protein signaling 2,RGS2）的影响,探讨地高辛治疗高血压性心肌肥厚的作用与可能的机制。方法30只雄性ApoE‐/‐小鼠随机分为对照组、AngⅡ模型组和AngⅡ＋Digoxin治疗组。所有小鼠从术前1 d至术后处死前均接受0.5％二甲基亚砜或地高辛溶液腹腔注射治疗,并且在术后28 d获取心脏组织,通过组织学检查、苏木精‐伊红（HE）染色切片分析技术评定心肌组织形态学变化、RGS2的mRNA及蛋白表达水平来评价地高辛的作用。结果与AngⅡ模型组相比,AngⅡ＋Digoxin组全心重量、左心室壁厚度、心肌细胞直径均明显减少（P＜0.05或 P＜0.01）,RGS2 mRNA变化不明显,而蛋白表达增高（P＜0.01）,心肌肥厚明显减轻。同时检测小鼠在术前3 d ,手术当天,术后3、7、14、28 d的血压,发现AngⅡ＋Digoxin组与AngⅡ模型组比较,术后7 d和14 d血压下降（均 P＜0.05）,术后28 d则差异无统计学意义。结论地高辛可能通过上调ApoE‐/‐小鼠高血压心肌肥厚模型RGS2的表达,有效减轻心肌肥厚,这说明地高辛可能在抑制心肌细胞肥大中起重要作用。     

亚降压剂量依那普利预防大鼠压力负荷性心肌肥厚的作用

目的：观察心脏肾素-血管紧张素系统（RAS）在压力负荷性心肌肥厚中的作用，并了解亚降压剂量转换酶抑制剂（ACEI）－依那普利对RAS和心肌肥厚的作用。方法：采用腹主动脉缩窄造成大鼠压力负荷升高，其中一组术前1天始予以亚降压剂量依那普利干预。于术后4周测定心脏局部血管紧张素Ⅱ（AngⅡ）、血浆AngⅡ、左室重量（LVW）、左室重量／体重比值（LVW／BW）、心肌细胞直径（DC）。结果：腹主动脉缩窄4周后实验手术组大鼠心肌局部AngⅡ（5．470132±0．52Pg／mg）较对照组（3．24±0.39Pg／mg）明显升高，且与LVW、LVW／BW、DC呈近相关（r分别为0．7152，0．8149，0．7528）；亚降压剂量依那普利干预后实验治疗组大鼠心肌局部AngⅡ，LVW，LVW／BW，DC均较手术组明显降低（3．48±0．41vs5．47±0．52pg／mg，438，9±4．22vs599．3±80.98mg，1.98±013vs2．64±0．19mg／g，16．45±0．4vs19．68±0．47um）；各组血浆AngⅡ无显著性差别（P＞0．05）结论：心肌局部RAS参与了大鼠压力负荷性心肌肥厚的发生发展过程；亚降压剂量依那普利能预防心肌肥厚的发生，并阻止心肌局部AngⅡ的升高。     

辛伐他汀对血管紧张素Ⅱ诱导的乳鼠心肌细胞肥大的保护作用及机制研究

目的 探讨辛伐他汀(simvastatin,Sim)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的心肌细胞肥大的保护作用及机制.方法 采用原代培养新生SD大鼠心肌细胞,以AngⅡ诱导心肌细胞肥大,观察Sim和环孢素A(cyclosporine A,CSA)对心肌肥厚的影响.应用计算机图像分析系统检测心肌细胞体积;考马斯亮蓝法测心肌细胞总蛋白;Till阳离子测定系统(德国)采用DM3000软件测定胞内[Ca2+]i瞬间变化;Western blotting法检测心肌细胞中钙调神经磷酸酶(calcineurin,CaN)蛋白的含量.结果 与AngⅡ组相比,Sim可以抑制AngⅡ诱导的细胞体积和总蛋白的增加(P＜0.05),抑制心肌细胞内钙离子浓度([Ca2+]i)瞬间变化幅度(P＜0.05),抑制CaN蛋白表达;Sim组与CsA(CaN抑制剂)组相比差异均无统计学意义.结论 Sim抑制AngⅡ诱导的心肌肥厚可能通过调节Ca2+/CaN通路发挥作用.     

荞麦花叶总黄酮对实验性大鼠心肌肥厚的保护作用

目的 探讨荞麦花叶总黄酮(TFBFL)对去甲肾上腺素所致大鼠心肌肥厚的保护作用及其可能的机制.方法 将大鼠随机分为6组(n=12)空白对照组,肥厚模型组,TFBFL Ⅰ、Ⅱ、Ⅲ组,和卡托普利治疗组(Cap组).用去甲肾上腺素(NE)腹腔注射1.5 mg(kg·d),Bid,建立大鼠心肌肥厚模型,同时TFBFL和Cap 灌胃给药100、200、400和50mg/(kg·d),o.d.,连续15 d.观察心电图(ECG),左心室肥厚指数(LVWIlvw/bw),和心重指数(HWIhw/bw,lvw/hw).采用比色法测定心室肌钙含量,用放免分析法检测血浆、心肌、肾脏血管紧张素Ⅰ(Ang Ⅰ)生成率(反映肾素活性)和血管紧张素Ⅱ(AngⅡ)含量.结果 与肥厚模型组比,TFBFL能剂量依赖性的改善心肌肥厚大鼠的ECG,降低LVWI和HWI,心肌钙含量和心肌Ang Ⅱ含量,但对血浆肾脏Ang Ⅱ含量无明显影响和心肌、血浆和肾脏AngⅠ生成率均无明显影响,且与阳性药物卡托普利组治疗效果相近.结论 荞麦花叶总黄酮对大鼠心肌肥厚具有保护作用,其机制可能与拮抗心肌局部肾素-血管紧张素(RAS)系统有关.     

过氧化物酶体增殖物激活受体γ在肥厚心肌中的表达及瑞舒伐他汀的干预作用

目的探讨过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptorγ,PPARγ）在大鼠心肌肥厚中的表达及瑞舒伐他汀抑制心肌肥厚的机制。方法 40只雄性SD大鼠随机分为4组：正常对照组、模型组、瑞舒伐他汀组和卡托普利组,每组10只。除正常对照组外,各组背部皮下注射异丙肾上腺素（isoproterenol,Iso）建立心肌肥厚模型。模型制备成功后,瑞舒伐他汀组灌胃给予瑞舒伐他汀4㎎/㎏.d,卡托普利组灌胃给予卡托普利50㎎/㎏.d,其余两组灌胃给予等体积生理盐水。四周末,分别测定各组大鼠左室收缩压（LVSP）、左室舒张末压（LVEDP）、左室压力上升及下降最大速率（±dp/dt max）;测定大鼠体重（BW）、心脏重量（HW）及左心室重量（LVW）,计算心脏重量指数（HWI）及左心室重量指数（LVWI）;应用病理学方法观察心肌组织形态学改变;Western-blot法测定心肌组织PPARγ蛋白表达。结果模型组大鼠LVEDP、HWI、LVWI明显高于正常对照组（P〈0.01）,LVSP和±dp/dt max明显降低（P〈0.01）;模型组PPARγ蛋白表达明显低于正常对照组（P〈0.01）;瑞舒伐他汀组和卡托普利组PPARγ蛋白表达明显高于模型组（P〈0.01）;瑞舒伐他汀组和卡托普利组比较,上述指标差异均无统计学意义（P〉0.05）。结论在大鼠心肌肥厚模型中PPARγ表达受抑制,瑞舒伐他汀通过增强PPARγ表达抑制心肌肥厚,改善心功能。     

肾性高血压大鼠肥大心肌bFGF与丝裂素活化蛋白激酶的表达及氯沙坦对其影响

目的:观察肾性高血压大鼠肥大心肌碱性成纤维细胞生长因子(bFGF)与丝裂素活化蛋白激酶(MAPK)表达的影响以及氯沙坦逆转心肌肥大的作用。方法:制备二肾一夹高血压大鼠模型为实验组,采用氯沙坦作为治疗组,以未进行二肾一夹大鼠作为假手术组,观察3组大鼠术后8周心肌肥大指数、心肌血管紧张素含量、心肌组织bFGF与MAPK的表达。结果:与假手术组相比,实验组大鼠术后8周心肌肥大指数、心肌Ang水平明显增高(分别P<0.01,P<0.05);治疗组大鼠心肌肥大指数则无明显差异,心肌Ang仍保持在高水平。与假手术组相比,实验组心肌bFGF与MAPK表达显著增强(分别P<0.05),而氯沙坦可以显著抑制bFGF与MAPK表达。结论:bFGF、MAPK参与肾性高血压心肌肥大的发生机制,氯沙坦除了阻断Ang诱导的肥大信号转导外,还可能通过抑制bFGF诱导的细胞信号转导途径逆转心肌肥大。     

血管紧张素(1-7)对压力负荷引起高血压大鼠心肌重构的影响

目的观察血管紧张素(1-7)[Ang-(1-7)]对压力负荷增高所致大鼠心肌重构的影响。方法 30只雄性SD大鼠随机分为3组:假手术组、腹主动脉缩窄(AAC)组和Ang-(1-7)组。后2组采用腹主动脉缩窄术建立心脏压力负荷增高动物模型。术后1 d开始,Ang-(1-7)组大鼠经渗透性微量泵持续颈静脉输注Ang(1-7)25μg·kg~(-1)·h~(-1),假手术组及AAC组经渗透性微量泵给予等量生理盐水。4周后鼠尾容积法测量收缩压;称取左心室质量(LVM),计算左心室质量指数(LVMI);HE染色检测心肌细胞平均直径;放免法测定血浆和心肌血管紧张素Ⅱ(AngⅡ)浓度。结果与假手术组相比,AAC组、Ang-(1-7)组收缩压、LVM、LVMI、心肌AngⅡ浓度、心肌细胞平均直径均显著升高(P<0.05,P<0.01)。与AAC组相比,Ang-(1-7)组血压和心肌AngⅡ浓度差异无统计学意义(P>0.05),但LVM、LVMI、心肌细胞平均直径明显降低(均P<0.05)。结论 Ang-(1-7)可改善腹主动脉缩窄高血压大鼠左室肥厚,逆转心肌重构。     

活血潜阳颗粒逆转自发性高血压大鼠左心室肥厚的实验研究

目的探讨活血潜阳颗粒逆转高血压左心室肥厚的作用机制。方法以自发性高血压大鼠(sponta-neoushypertensionrats,SHR)为高血压及高血压左心室肥厚模型,随机分为活血潜阳颗粒高、中、低剂量治疗组,卡托普利治疗组,松龄血脉康治疗组和模型组,并以正常血压Wistar-Kyoto大鼠为正常对照组,检测大鼠尾动脉收缩压(systolicbloodpressure,SBP)及左心室质量指数(leftventricularmassindex,LVMI),放免法测定大鼠左心室组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)含量,应用免疫组化法、RT-PCR法观察左心室组织血管紧张素转换酶(angiotensinconvertingenzyme,ACE)蛋白与mRNA表达。结果(1)与正常对照组比较,模型组SBP、LVMI值显著升高;与模型组比较,活血潜阳颗粒高、中剂量可显著降低SBP、LVMI值,其作用与松龄血脉康治疗组比较,差异无统计学意义,但作用明显差于卡托普利治疗组;(2)与正常对照组比较,模型组左心室组织AngⅡ含量升高,ACE蛋白、mRNA表达明显上调;与模型组相比,活血潜阳颗粒高、中、低剂量可减少心脏局部AngⅡ的含量,下调SHR左室心肌ACE蛋白及mRNA表达,其下调作用与松龄血脉康治疗组比较,差异无统计学意义,但其作用明显不及卡托普利治疗组。结论活血潜阳颗粒可逆转SHR左心室肥厚,其作用机制可能与下调左室心肌ACE蛋白及mRNA的表达,减少心脏局部AngⅡ的含量有关。     

氯沙坦对急性容量和压力超负荷心肌肥大的逆转作用

目的:观察AngⅡ1型受体(ATl)拮抗剂氯沙坦(Losartan)的逆转急性容量和压力超负荷心肌肥大(MH)作用。方法:选择60只雄性SD大鼠,每组12只,随机分为5组:腹腔动静脉造瘘容量超负荷组(VO组);容量超负荷+治疗组(LOSV组):腹主动脉部分结扎压力超负荷组(PO组);压力超负荷+治疗组(LOSP组)及对照组(CON组)。对比检测术后第10天和第20天的收缩压(SBP)、左室重量指数(LVMI)、心肌及血浆AngⅡ含量。电镜观察第20天心肌超微结构变化。结果:①两模型组LVMI、SBP及心肌AngⅡ第10天和第20天均显著升高(P<0.05,与CON组比),而血浆AngⅡ均仅于第20天才较对照组明显升高(P<0.05);②AT1受体被阻断后第10天,两治疗组LVMI及SBP较各自未治疗组均明显下降(P<0.05)(LOSP组LVMI下降幅度无统计学意义),但仍高于CON组(P<0.05)。LOSV组和LOSP组心肌AngⅡ较各自未治疗组均有升高,前者有统计学差异(P<0.05,与VO组比较)。两治疗组血浆AngⅡ较未治疗组均明显升高(P<0.05);③ATl受体被阻断后第20天,两治疗组LVMI、SBP和LOSP组心肌AngⅡ较各自未治疗组均明显降低(P<0.05),LOSV组心肌AngⅡ下降不明显(P>0.05),上述指标均高于CON组(P<0.05)。两治疗组血浆AngⅡ较各自未治疗组明显升高(P<0.05)。电镜示两治疗组心肌线粒体空泡样化较各自未治疗组均明显好转;④两模型组LVMI与心肌AngⅡ及血浆AngⅡ均呈显著正相关(P<0.01),前者相关强度高于后者。结论:AT1受体拮抗剂Losartan早期具显著逆转MH作用。     

鞘磷脂合酶抑制剂对血管紧张素Ⅱ诱导的高血压小鼠心肌纤维化的影响

目的 研究鞘磷脂合酶抑制剂D609对血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）诱导的心肌纤维化的影响。方法 将雄性野生型C57BL/6J小鼠28只,采用随机数字表区组分组法分为对照组、D609组、AngⅡ组和AngⅡ+D609组,每组7只。通过持续皮下灌注AngⅡ建立高血压模型,2周后观察小鼠的血压变化,行心脏超声评估心脏结构和功能。采用HE与Masson染色观察心肌纤维化。使用ELISA方法测定小鼠血浆中炎性反应因子、肿瘤坏死因子（tumor necrosis factor-α,TNF-α）及白细胞介素（interleukin-6,IL-6）的浓度。结果 与对照组小鼠比较,AngⅡ组小鼠血压出现显著升高和心肌肥厚,而且心肌纤维化明显增加,血浆中TNF-α及IL-6的浓度显著增加。与AngⅡ组比较,AngⅡ+D609组小鼠血压降低,心肌肥厚明显减轻,心肌及血管组织的胶原纤维沉积显著减少,且血浆TNF-α及IL-6的浓度显著降低。结论 鞘磷脂合酶在高血压导致的心肌纤维化中可能发挥重要作用。     

Changes in Cold and Hot Syndromes and Gastrointestinal Bacterial Community Structure in Mice by Intervention with Food of Different Nature

Objective: To reveal the effect of foods with different natures on cold or hot syndrome and gastrointestinal bacterial community structure in mice. Methods: Forty-five 6-week-old male ICR Kunming mice of clean grade were divided into 5 groups, 9 per group, including the control (CK), hot nature herb medicine(HM), Hong Qu glutinous rice wine (RW), tea rice wine (TW), and cold nature herb medicine (CM) groups. Distilled water or corresponding herbs were administered to mice (0.01 mL/g body weight) in the 5 groups by gastric infusion respectively, once daily for 28 d. Appearance, behavior, and serum biochemical indicators, including 5-hydroxytryptamine (5-HT), thyroid stimulating hormone (TSH), noradrenaline (NE), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), the hot nature index, as well as the gastrointestinal bacterial community structure were analyzed in all groups after treatment. Results: After supplementation for 28 d, CM and TW mice showed different degrees of cold syndrome, and HM and RW mice showed different degrees of hot syndrome. Compared with the HM and RW mice, the TSH, NE, cAMP levels and hot nature indices in the CM and TW mice were significantly decreased and 5-HT and cGMP levels were significantly increased (P<0.05). There was no obvious change in appearance or behavior in CK mice. Results of clustering analysis showed that the gastrointestinal bacterial community structures were highly similar in TW and CM mice as well as in RW and HM mice, and that they were from the same branch, respectively, when the distance was 0.02. The key microbes associated with cold syndrome were Lachnospiraceae uncultured, Lactococcus, etc., and the key microbes associated with hot syndrome were S24-7 norank, Ruminococcaceae uncultured, etc. Conclusion: The interventions with different nature foods could change cold or hot syndrome in mice, leading to changes in gastrointestinal bacterial community structure.     

Apoptosis, myocardial fibrosis and angiotensin Ⅱ in the left ventricle of hyp ertensive rats treated with fosinopril or losartan

Objective To investigate the different effects of an angiotensin Ⅱ type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin Ⅱ (AngⅡ) in the left ventricle of spontaneously hypertensive rats (SHRs). Methods SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg·kg(-1)·d(-1)), SHR-F (treated with fosinopril, 10 mg·kg(-1)·d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and AngⅡ concentrations of plasma and myocardium were examined. Results Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang Ⅱ levels were significantly increased in the losartan group. However, plasma Ang Ⅱ concentrations were not altered, and myocardium AngⅡ concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group. Conclusions Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.     

Effect of Sodium Tanshinone ⅡA Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinasel/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective： To observe the effects of sodium tanshinone ⅡA sulfonate （STS） on angiotensin Ⅱ （Ang Ⅱ）-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase （p-ERK1/2）. Methods： In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling. Results： （1） The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ （1 μ mol/L） for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein. （2） After pretreatment of myocardial cells with Ang Ⅱ （1 μmol/L） for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses （2, 10, 50μmol/L） for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner. （3） After the myocardial cells were stimulated by AngⅡ （1 μ mol/L）, the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS. （Conclusion： STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.