血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动脉收缩中的作用

以黄嘌岭(X)-黄嘌呤氧化酶(XO)系统产生氧自由基,应用微量生物测定法观察慢性缺氧(5000m,10d)对大鼠氧自由基所致肺内动脉收缩的影响及内皮舒张因子(EDRF)在其中的作用。慢性缺氧大鼠有内皮的肺内动脉环对氧自由基的收缩反应较正常环境中的对照动物明显增强,加入EDRF灭活剂还原型血红蛋白(RHb)后更加显著;而加入超氧化物歧化酶(铜锌SOD)后则减弱,甚至消除。反之,不论加入RHb或SOD对氧自由基所致去内皮肺内动脉环的收缩反应均无明显影响。上述结果表明慢性缺氧引起肺内动脉收缩增强与EDRF有密切关系:慢性缺氧可能使EDRF的作用减弱,肺内动脉对氧自由基的反应性增强。表示EDRF及其与氧自由基的关系在慢性缺氧性肺动脉高压的形成中可能具有十分重要的意义。     

抗氧化剂丹酚酸A对缺氧鼠肺内动脉ACh舒张反应的影响

应用微量生物测定法观察了丹酚酸A(salvinolic acid A,Sal.A)对慢性缺氧(5000m,10d)大鼠(200～300g)肺内动脉ACh舒张反应的影响,并对其机制进行了初步探讨。实验发现,慢性缺氧可明显减弱大鼠肺内动脉ACh(10~(-8)～10~(-4)mol/L)舒张反应(P<0.01～0.001),在浴槽内先加入Sal.A(10~(-4)mol/L),缺氧鼠肺内动脉ACh舒张反应明显增强(P<0.01),而在浴槽内同时加入血管内皮舒张因子(EDRF)灭活剂phenidon(5×10~(-5)mol/L),则Sal.A上述增强缺氧鼠肺内动脉ACh舒张反应的作用消失。此外,本实验还发现,在以黄嘌呤(X,10~(-4)mol/ L)-黄嘌呤氧化酶(XO,0.01U/ml)系统产生氧自由基损伤正常大鼠肺内动脉ACh舒张反应的基础上,Sal.A(10~(-4)mol/L)同样可明显减弱氧自由基对大鼠肺内动脉ACh舒张反应的损伤作用。结果表明,Sal.A可消除氧自由基对肺血管内皮细胞释放的EDRF的破坏作用而具有保护慢性缺氧鼠肺内动脉ACh舒张反应的作用。     

急性缺氧所致大鼠肺动脉内皮依赖性收缩反应

本实验初步证实,急性缺氧可使大鼠肺动脉产生内皮衍生收缩因子,并对其性质作了初步探讨。急性缺氧可使离体大鼠肺内和肺外动脉产生收缩反应,当灌流液氧分压从约17.3kPa降低到4kPa时(pH7.40～7.48),肺内和肺外动脉的基础张力分别比原来静息张力增加了37.5±5.1mg(n=4)和33.2±1.9mg(n=6);当氧分压恢复到约17.3kPa时,肺动脉基础张力也降到缺氧前的静息张力水平,即肺内动脉约300mg,肺外动脉约400mg。去掉内皮细胞后,急性缺氧引起的肺动脉收缩反应消失。消炎痛、去甲二氢愈创木脂酸、阿托品和酚妥拉明均不能阻断急性缺氧所致大鼠肺动脉内皮依赖性收缩反应。急性缺氧可诱发大鼠肺动脉内皮细胞产生释放非花生四烯酸环氧酶和脂氧酶代谢产物的内皮衍生收缩因子。     

慢性缺氧对肺动脉内皮依赖性和非内皮依赖性舒张反应的影响

本实验用生物测定法观察了模拟海拔5000m高度连续缺氧20d对大鼠肺动脉内皮依赖性和非内皮依赖性舒张反应的影响。结果显示慢性缺氧明显抑制了肺内和肺外动脉对乙酰胆碱、ATP、硝普钠和异丙肾上腺素舒张反应的敏感性和反应性。在浓度为10~(-6)mol/L时,缺氧组大鼠肺内动脉对乙酰胆碱、硝普钠和异丙肾上腺素的舒张反应分别只有对照组大鼠的61.3％、75.9％和61.7％,对浓度为1.8×10~(-5)mol/L的ATP的舒张反应只有对照组大鼠的64.9％。研究表明,ATP和乙酰胆碱主要是通过内皮舒张因子使肺动脉产生内皮依赖性舒张反应,硝普钠和异丙肾上腺素分别通过直接激活血管平滑肌细胞鸟苷酸环化酶和β受体使血管产生非内皮依赖性舒张反应。缺氧同时抑制了肺动脉内皮依赖性和非内皮依赖性舒张反应,提示慢性缺氧可能抑制了正常肺内舒血管活性物质的生理作用。     

慢性缺氧对大鼠肺动脉内皮依赖性舒张反应及cGMP含量的影响

本实验观察了慢性缺氧对大鼠肺动脉内皮依赖性舒张反应和肺动脉内环磷酸鸟苷(cGMP)含量的影响。乙酰胆碱(ACh)和三磷酸腺苷(ATP)可使正常大鼠的离体肺动脉产生内皮依赖性舒张反应,其舒张作用不受消炎痛的影响,但被甲烯蓝完全抑制。慢性缺氧明显减低了 ACh 和 ATP 诱发的大鼠肺内和肺外动脉的内皮依赖性舒张反应。当 ACh 浓度为10~(-6)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张百分数分别为对照组的61.3%和59.2%;当 ATP浓度为1.8×10~(-5)mol/L 时,缺氧组大鼠肺内和肺外动脉舒张反应分別为对照组的64.9%和55.3%。慢性缺氧也减低了硝普钠(SNP)诱发的大鼠肺动脉非内皮依赖性舒张反应。慢性缺氧显著减低了大鼠肺动脉内 cGMP 的含量。缺氧组和对照组大鼠肺动脉内 cGMP 的基础含量分别是51.9±5.7 pmol/g wet wt.(n=14)和84.9±9.7 pmol/g wet wt.(n=14),p<0.01;经 10~(-7)mol/L ACh 刺激后分别是91.4±7.3 pmol/g wet wt.(n=5)和240.8±30.6pmol/g wet wt.(n=5),p<0.01。慢性缺氧可能抑制了肺动脉平滑肌细胞胞浆中可溶性鸟苷酸环化酶,从而减低了肺动脉对内皮舒张因子和 SNP 的舒张反应性。     

生长抑素对氧自由基引起的离体胃粘膜细胞损伤的保护作用及其机制

采用pronase—EDTA法分离大鼠胃粘膜细胞,将黄嘌呤氧化酶(xanthineoxidase,XO)—黄嘌呤(xanthine,X)氧自由基生成系统加入培养液诱发细胞的损伤。观察到预先加入生长抑素可以剂量依赖性地减轻XO—X引起的细胞死亡和乳酸脱氢酶的漏出;同时抑制XO—X引起的细胞脂质过氧化水平的升高,并翻转细胞膜流动性及溶血性卵磷脂与卵磷脂比值的变化。上述结果提示,生长抑素对氧自由基引起的胃粘膜细胞损伤可能具有直接的保护作用,其机制似与防止质膜的脂质过氧化并从而保护细胞膜免受损伤有关。     

川芎嗪对慢性缺氧大鼠肺动脉和主动脉的离体舒张作用

用生物测定法观察了川芎嗪对慢性缺氧大鼠肺动脉和主动脉环的舒张效应,并与乙酰胆碱的舒血管作用进行了比较。结果表明:川芎嗪对慢性缺氧大鼠肺动脉和主动脉的舒张作用均与平原组无明显差异。慢性缺氧明显减低了乙酰胆碱诱发的肺动脉内皮依赖性舒张反应,但不影响川芎嗪对肺血管的舒张作用。提示川芎嗪对肺血管的舒张作用不依赖于内皮。川芎嗪对肺动脉的舒张作用明显大于体动脉。这些特性有利于川芎嗪对肺动脉高压的治疗。     

埃他卡林对低氧暴露大鼠脑和肺微动脉选择性扩张作用

目的:研究低氧暴露对大鼠脑和肺微动脉内皮功能的影响以及埃他卡林(Ipt)对以上微动脉的扩张作用特征。方法:将雄性SD大鼠随机分为2组,常压常氧组(control)和低氧暴露组(hypoxic),后者置于常压低氧暴露舱内(O27.8%)8 h。分离大鼠管径为(204±5)μm的脑基底动脉、肺微动脉组织,利用DMT微血管张力测定仪在6nmol/L内皮素-1(ET-1)致血管预收缩条件下,利用乙酰胆碱(ACh)考察微动脉内皮功能及观察不同浓度Ipt对脑和肺微动脉张力变化的影响。结果:与常压常氧组对比,10-5 mol/L乙酰胆碱(ACh)对低氧暴露脑肺微动脉扩张率显著降低(P0.05);新型ATP敏感性钾通道开放剂Ipt在(10-11~10-3)mol/L对低氧暴露肺微动脉呈剂量依赖性扩张作用,明显强于对常压常氧组(P0.01),在(10-11~10-3)mol/L对低氧暴露脑微动脉呈剂量依赖性扩张作用,但与常压常氧组相比无显著差异。结论:低氧暴露可导致脑基底动脉和肺微动脉内皮功能受损,Ipt具有选择性增强扩张低氧暴露肺微动脉的作用,但不影响以上条件低氧暴露后脑基底动脉的扩张作用,提示该药可应用于改善低氧暴露所致的肺微血管收缩,为Ipt发展为新型治疗肺动脉高压的药物提供理论基础。     

巯基物质在氧自由基损伤离体胃粘膜细胞中的作用

本文用离体胃粘膜细胞研究了细胞内流基物质在活性氧诱发细胞损伤中的作用。实验采用pronase-EDTA法分离大鼠胃粘膜细胞并进行短期孵育,以黄嘌呤氧化酶(XO)-黄嘌呤(X)系统产生氧自由基损伤细胞。实验结果表明,用XO-X损伤胃粘膜细胞时,细胞存活率显著降低,乳酸脱氨酶(LDH)漏出量增多,同时细胞内非蛋白质巯基(NPSH)和蛋白质巯基(PSH)含量均不同程度地下降;N-乙基顺丁烯二酰亚胺(NEM)在耗竭细胞内NPSH和PSH的同时,引起细胞死亡和LDH漏出增加,这一作用与NEM的作用时间和浓度是显著依从关系;在细胞孵育液中预先加入含-SH的化合物还原型谷胱甘肽(GSH)或半胱胺,可剂量依赖性地减轻XO-X引起的细胞损伤。上述结果提示,胃粘膜细胞内的巯基物质在自身防御机制中具有重要作用,氧自由基损伤胃粘膜细胞的机制之一可能与破坏细胞内巯基的稳态有夫。     

大、小动脉内皮细胞乙酰胆碱作用靶标药理学特性的比较

目的 :比较大、小动脉内皮细胞乙酰胆碱作用靶标药理学特性的差异。方法 :采用大鼠尾动脉螺旋状血管条和主动脉离体血管环两种组织 ,对比观察乙酰胆碱 (ACh)诱发大、小动脉内皮依赖性舒张反应特征的差异 ,从而进一步研究小动脉内皮细胞乙酰胆碱作用靶标的药理学特性。结果 :氯化钾 (6 0mmol/L)预致血管收缩的尾动脉和主动脉对不同浓度ACh (10 -8～ 10 -4mol/L)产生内皮依赖性舒张反应 ,且呈剂量依赖性。L Nω 硝基精氨酸甲酯 (L NAME :10 -4mol/L)或美蓝 (MB :10 -5mol/L)与吲哚美辛 (Indo :10 -4mol/L)联用仅可部分地阻断ACh诱发尾动脉内皮依赖性舒张反应 ;而L NAME或MB可完全阻断ACh诱发主动脉内皮依赖性舒张反应。结论 :ACh激活大、小动脉上内皮细胞乙酰胆碱作用靶标诱发内皮依赖性舒张反应的药理学性质不同 ,在小动脉上 ,除了NO和PGI2介导外 ,还有一种非NO和非PGI2 的舒血管因子参与 ;在大动脉上 ,内皮依赖性舒张反应主要由NO介导     

Entwicklungsgeschichte und Ultrastruktur von Pollenkitt und Exine bei nahe verwandten entomophilen und anemophilen Angiospermensippen derAlismataceae,Liliaceae, Juncaceae,Cyperaceae, Poaceae undAraceae

Some closely related members of the monocotyledonous familiesAlismataceae, Liliaceae, Juncaceae, Cyperaceae, Poaceae andAraceae with variable modes of pollination (insect- and wind-pollination) were studied in relation to the ultrastructure of pollenkitt and exine (amount, consistency and distribution of pollenkitt on the surface of pollen grains). The character syndromes of pollen cementing in entomophilous, anemophilous and intermediate (ambophilous or amphiphilous) monocotyledons are the same in principal as in dicotyledons. Comparing present with former results one can summarize: 1) The pollenkitt is always produced in the same manner by the anther tapetum in all angiosperm sub-classes. 2) The variable stickiness of entomophilous and anemophilous pollen always depends on the particular distribution and consistency of the pollenkitt, but not its amount on the pollen surface. 3) The mostly dry and powdery pollen of anemophilous plants always contains a variable amount of inactive pollenkitt in its exine cavities. 4) A step-by step change of the pollen cementing syndrome can be observed from entomophily towards anemophily. 5) From the omnipresence of pollenkitt in all wind-pollinated angiosperms studied one can conclude that the ancestors of anemophilous angiosperms probably have been zoophilous (i.e. entomophilous) throughout.

     

Identification and Characterization of the First Equine Parainfluenza Virus 5

正Dear Editor,Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative-sense,nonsegmented, single-stranded RNA virus belonging to the Paramyxoviridae family (Chen 2018). The virus was first reported in primary monkey kidney cells in 1954 (Hsiung1972), then it has been frequently discovered in various     

Pathogenic Characterization and Full Length Genome Sequence of a Reassortant Infectious Bursal Disease Virus Newly Isolated in Pakistan

<正>Dear Editor,Infectious bursal disease (IBD) is one of the most important diseases of the poultry. The IBD virus (IBDV), a nonenveloped virus belonging to the Birnaviridae family with a genome consisting of two segments of double-stranded RNA (segments A and B), targets B lymphocytes of bursa of Fabricious leading to immunosuppression. In Pakistan,poultry farming is the second biggest industry and IBD is the second biggest disease threating the poultry sector.However, there is limited genome information of IBDV     

Mink Circovirus Can Infect Minks,Foxes and Raccoon Dogs

正Dear Editor,Mink circovirus (MiCV), which is clustered in the genus Circovirus of the family Circoviridae, was first described in minks from farms in Dalian, China in 2013 (Lian et al.2014). The complete single-stranded circular genome of the virus is 1,753 nucleotides long and contains two major open reading frames (ORFs), designated ORF1 (Rep gene)and ORF2 (Cap gene)(Lian et al. 2014; Ge et al. 2018).Sequence analysis has shown that MiCV is most closely     

CypA Regulates AIP4-Mediated M1 Ubiquitination of Influenza A Virus

Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin–proteasome-mediated degradation of M1. However,the mechanism by which CypA regulates M1 ubiquitination remains unknown. In this study, we reported that E3 ubiquitin ligase AIP4 promoted K48-linked ubiquitination of M1 at K102 and K104, and accelerated ubiquitin–proteasome-mediated degradation of M1. The recombinant IAV with mutant M1 (K102 R/K104 R) could not be rescued, suggesting that the ubiquitination of M1 at K102/K104 was essential for IAV replication. Furthermore, CypA inhibited AIP4-mediated M1 ubiquitination by impairing the interaction between AIP4 and M1. More importantly, both the mutations of M1 (K102 R/K104 R) and CypA inhibited the nuclear export of M1, indicating that CypA regulates the cellular localization of M1 via inhibition of AIP4-mediated M1 ubiquitination at K102 and K104, which results in the reduced replication of IAV.Collectively, our findings reveal a novel ubiquitination-based mechanism by which CypA regulates the replication of IAV.