心肌肥厚大鼠心肌Cx43的表达及法舒地尔的干预作用

目的：研究腹主动脉缩窄大鼠心肌缝隙连接蛋白Cx43的变化及法舒地尔的干预作用。方法：腹主动脉缩窄建立心肌肥厚大鼠模型,随机分假手术组,腹主动脉缩窄组、腹主动脉缩窄＋10mg／kg法舒地尔（ip,每天1次,8周）组、腹主动脉缩窄＋40mg／kg（ip,每天1次,8周）。病理切片观察心肌组织学变化;免疫组化法检测心肌Cx43蛋白表达。结果：模型组大鼠心肌细胞排列紊乱,肥大,间隙增宽,Cx43蛋白表达量明显低于正常组;Fas治疗后,死亡率下降,cx43蛋白表达量高于模型组,差异具有统计学意义（P〈0．01）。结论：Fas可能通过调高Cx43蛋白表达,治疗大鼠心肌肥厚。     

穿心莲内酯对大鼠心肌肥厚的影响

研究穿心莲内酯(AP)对由腹主动脉缩窄所致大鼠心肌肥厚的抑制作用。采用腹主动脉缩窄法制备大鼠心肌肥厚模型,10天后开始每天一次的AP0.5,1.0,2.0g/kg给药,共10周。测定心脏质量指数(HMI)、左心室质量指数(LVMI);检测血清及心肌组织的乳酸脱氢酶(LDH)和左心室心肌组织乳酸(LAC)、游离脂肪酸(FFA)含量。同假手术组相比,心肌肥厚模型组大鼠心肌组织LDH明显降低,其他指标明显升高;AP低中高给药组中,中、高剂量组各个指标明显改善。AP对心肌肥厚具有较好抑制作用,其具体原因可能与调节心肌细胞产能机制有关。     

心肌营养素-1和结缔组织增长因子在糖尿病大鼠心肌中的表达及厄贝沙坦的干预作用

目的通过观察心肌营养素-1（CT—1）mRNA和结缔组织增长因子（CTGF）在糖尿病大鼠心肌中的动态表达以及厄贝沙坦干预的影响,探讨CT—1和CTGF在糖尿病心肌病（DMCM）发病机制中的作用。方法SD雄性大鼠78只,随机分为对照组和糖尿病组。用链脲佐菌素（STZ）一次性腹腔注射建立糖尿病模型后,糖尿病组再为厄贝沙坦治疗组及糖尿病未治疗组。治疗组以厄贝沙坦灌服12周。分别在病程2、4、6、8、10、12周处死各组大鼠。称量体重（BW）、全心重量（HW）、左室重量（LVW）,计算心体比（HW／BW）和左室重量指数（LVWI）。检测心肌CT—1 mRNA和CTGF的表达水平;心肌胶原（Col）和心肌血管紧张素（AngⅡ）含量。观察心肌超微结构病理改变。结果糖尿病组大鼠的HW／BW、LVWI明显高于正常对照组（P〈0．01）,厄贝沙坦治疗组大鼠的HW／BW、LVWI明显低于糖尿病组（P〈0．01）,但仍高于正常对照组（P〈0．01）。厄贝沙坦组心肌细胞变性、坏死程度和范围较糖尿病组明显减轻。糖尿病组大鼠CT—1 mRNA、CTGF表达明显卜调,随病程延长呈升高趋势（P〈0．01）,心肌col、AngⅡ含量较正常对照组明显升高（P〈0．01）。而厄贝沙坦治疗组大鼠的CTI mRNA、CTGF表达与糖尿病组相比较下调（P〈0．01）;心肌Col、AngⅡ含量明显低于糖尿病组（P〈0．05）。糖尿病组大鼠心室CT—1mRNA、CTGF和心室局部Col、AngⅡ含量呈明显正相关。结论糖尿病大鼠心肌CT—1mRNA、CTGF表达上调与心肌肥大、间质纤化密切相关,在糖尿病心肌病的心室重构中起重要作用。厄贝沙坦町减轻糖尿病心肌病的心室重构,其心肌保护作用机制可能与其下调CT—1和CTGF水平有关。     

压力负荷型心肌肥厚大鼠心肌组织相关基因的分离

心肌肥厚是心血管疾病常见的临床并发症 ,与冠心病、心衰、脑卒中等心血管疾病密切相关[1] ,其发生机制目前仍不清楚 .探讨其机制将为心肌肥厚及相关疾病的研究和治疗提供有益的线索 .本研究选用腹主动脉绑扎的左心室肥厚大鼠模型 ,运用差减杂交法 ,研究其中相关基因的表达变化 .1　材料和方法1 .1　压力负荷型左心室肥厚大鼠模型采用腹主动脉缩窄法[2 ] :雄性健康 Wistar大鼠 ( 2 0 0 g左右 )用速眠新 846合剂麻醉 ,将直径 0 .7mm的小圆棒以3/0丝线绕腹主动脉一起绑紧 ,抽出小圆棒 .对照组行假手术 .大鼠血压测量采用颈动脉插管 (术后 2 8…     

有氧运动改善自发性高血压大鼠肾纤维化的作用*

目的: 研究有氧运动训练对自发性高血压大鼠(SHR)肾脏纤维化影响, 探讨有氧运动对高血压肾损害的保护作用。方法: 8周龄雄性SHR和同龄Wistar京都大鼠(WKY)随机分为4组(n=6):安静WKY对照组(WKY-S)、安静SHR对照组(SHR-S)、低强度运动组(SHR-L)和中强度运动组(SHR-M)。SHR-L组、SHR-M组分别以14 m/min(最大有氧速度的35%)、20 m/min(最大有氧速度的50%)在0°坡度的运动跑步机上跑步,共运动14周,每周5次,每次60 min,WKY-S和SHR-S组安静饲养。14周后,运动训练结束72 h后检测大鼠血压;之后取血和肾脏检测血清肌酐SCr和尿素氮BUN含量,苏木精与伊红(HE)染色观察肾组织形态,Masson染色观察肾组织胶原沉积情况,计算肾脏胶原容积分数(CVF),检测肾脏 AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达。结果: 与WKY-S组相比,SHR-S组的血压和血清SCr、BUN含量、肾脏CVF水平和AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达均明显升高(P＜0.05);与SHR-S组相比,SHR-L组和SHR-M组血压和血清SCr、BUN含量、肾脏CVF水平和AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达均明显下降(P＜0.05)且SHR-M组下降趋势更明显(P＜0.05)。结论: 有氧运动可通过抑制肾脏AngⅡ-AT1R-TGF-β通路,改善自发性高血压大鼠的肾纤维化与肾功能。     

多重干预RAAS对大鼠慢性心功能不全心室重构及血钾的影响

目的探讨多重干预RAAS对大鼠慢性心功能不全心室重构及血钾的影响。方法实验采用缩窄大鼠腹主动脉法建立慢性压力负荷致心功能不全动物模型,选6周龄20只雌性SD大鼠,随机分4组(每组5只),B组(手术模型组)、C组(卡托普利组)、D组(卡托普利+缬沙坦组)、E组(卡托普利+缬沙坦+螺内酯组),另随机抽取5只同龄雌性SD大鼠假手术作为对照(A组)。给药8周后用Doppler超声心动图检测大鼠心脏结构和心功能各项参数的变化,放射免疫法测定血浆AngⅡ,ALDO浓度,并生化检测血钾水平。结果腹主动脉结扎后第9周,与A组比较,B组舒张末期室间隔厚度(IVSTD)、舒张末期左室后壁厚度(LVPWTD)、相对室壁厚度(RWT)、左室重量(LVM)、左室重量与体重比(LVM/BW)均显著提高(P<0.05);C、D、E组与B组相比,LVM,LVM/BW下降显著(P<0.05)。各药物干预组(C、D、E)血浆AngⅡ,ALDO水平明显低于B组(P<0.05),以联合应用螺内酯组明显。各药物干预组与A组和B组相比较,血钾水平差异无显著性(P>0.05)。结论联合应用卡托普利、缬沙坦及螺内酯多重干预RAAS能明显改善大鼠慢性心功能不全心室重构,对血钾无明显影响。     

慢性充血性心力衰竭大鼠模型的建立

目的:探讨建立慢性充血性心力衰竭大鼠模型的方法。方法:采用腹主动脉缩窄法制备CHF大鼠模型。于右肾动脉分支处上方缩窄腹主动脉至0.6mm,同时设立假手术组及正常对照组。12周后行一般情况观察,超声心动图及血液动力学检测心脏结构和功能、计算心脏肥厚指数,HE及Masson染色检测心肌病理改变,综合评价CHF大鼠心功能。结果:与假手术及正常对照组比较,CHF模型组术后12周均出现进食减少、精神萎靡、少动、被毛无光;IVS、LVPW、LVM、LVEDD、LVESD、SV显著增加,EF、FS显著降低;HR显著增加;VSP、+dP/dtmax显著降低,T-dP/dtmax显著延长;LVEDP显著升高,-dP/dtmax绝对值显著降低;心脏湿重及心脏肥厚指数均增加;病理结果表明CHF模型组心肌细胞肥大、排列紊乱、心肌胶原纤维增多。结论:应用腹主动脉缩窄术可成功制备CHF大鼠模型。     

慢性充血性心力衰竭大鼠模型的建立

目的：探讨建立慢性充血性心力衰竭大鼠模型的方法。方法：采用腹主动脉缩窄法制备CHF大鼠模型。于右肾动脉分支处上方缩窄腹主动脉至0.6mm,同时设立假手术组及正常对照组。12周后行一般情况观察,超声心动图及血液动力学检测心脏结构和功能、计算心脏肥厚指数,HE及Masson染色检测心肌病理改变,综合评价CHF大鼠心功能。结果：与假手术及正常对照组比较,CHF模型组术后12周均出现进食减少、精神萎靡、少动、被毛无光;IVS、LVPW、LVM、LVEDD、LVESD、SV显著增加,EF、FS显著降低;HR显著增加;VSP、＋dP/dtmax显著降低,T-dP/dtmax显著延长;LVEDP显著升高,-dP/dtmax绝对值显著降低;心脏湿重及心脏肥厚指数均增加;病理结果表明CHF模型组心肌细胞肥大、排列紊乱、心肌胶原纤维增多。结论：应用腹主动脉缩窄术可成功制备CHF大鼠模型。     

压力后负荷增高大鼠心肌肥厚向心力衰竭的转变

目的观察单纯腹主动脉缩窄造成的心肌肥厚能否转变成为心力衰竭。方法实验选用8周龄的Wistar大鼠,使用7-0号尼龙线对其肾上腹主动脉进行缩窄手术,造成后负荷性心肌肥厚模型(LVH,n=10),同时设置假手术组(Sham,n=10)和正常组(Con,n=10)作为对照。术后第20周和第38周使用超声多普勒和多导生理仪对大鼠血流动力学进行检测。解剖后取出心脏,计算心脏/体重比,并通过HE染色和天狼猩红染色观察心脏形态和纤维化程度。结果腹主动脉结扎后第20周,LVH组大鼠心室壁肥厚,舒张功能下降(E/Aratio:LVH组:1.0±0.25,Con组:1.6±0.12)。术后38周,左心室壁肥厚程度有所下降,但是心室腔扩大,心脏收缩和舒张功能明显下降(EF:LVH组:44.8±8.42,Con组:70.9±5.19;MaxdP/dt:LVH组:4916±1267.3,Con组:14225±932.1;MindP/dt:LVH组:-3246±1217.3,Con组:-12138±725.2)。腹主动脉缩窄术后的动物心脏重量明显增加(3.58±0.32vs.2.34±0.15),HE染色和天狼猩红染色显示LVH组大鼠在术后38周心脏纤维化明显。结论腹主动脉缩窄造成的后负荷增高动物模型首先出现向心性心肌肥厚,伴以舒张功能下降,进而收缩功能下降,发展为心力衰竭。     

细胞核CaMK和Calcineurin 对大鼠心肌肥厚发生的作用

目的:研究大鼠心肌肥厚时,钙依赖的蛋白激酶和蛋白磷酸酶在心肌细胞膜、细胞浆和细胞核的分布规律,以探讨核钙信号与核反应在心肌肥厚发生过程中的病理生理意义.方法:制备腹主动脉缩窄大鼠心肌肥厚模型,同位素32P掺入法分别测定心肌细胞核、细胞浆和细胞膜的蛋白激酶活性及用无机磷生成显色法测定其蛋白磷酸酶活性.结果:腹主动脉缩窄术后4周大鼠心肌显著肥厚,伴有明显的血液动力学异常.与正常对照组相比较,腹主动脉缩窄心肌肥厚组心肌细胞核钙调素蛋白激酶(CaMK)活性增加101.1%(P＜0.01),其膜的酶活性升高40.2%(P＜0.01),而胞浆的酶活性不变(P＞0.05);心肌细胞核钙调神经磷酸酶(Calcineurin)活性增加43.6%(P＜0.05),膜和胞浆中其活性增加无显著性(P＞0.05).正常组和腹主动脉缩窄心肌肥厚组心肌细胞CaMK和Calcineurin活性分布为核＞膜＞胞浆(P＜0.01).结论:腹主动脉缩窄心肌肥厚时核内钙依赖的CaMK和Calcineurin活性增加,提示压力超负荷时细胞核内钙调节的蛋白磷酸化和去磷酸化水平增高,可能在介导心肌肥厚的发生中起重要作用.     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.