p38MAPK信号通路介导右美托咪定对缺氧/复氧心肌细胞损伤的保护作用

目的探讨右美托咪定(Dex)是否通过p38丝裂原活化蛋白激酶(MAPK)信号通路发挥对缺氧/复氧(H/R)心肌细胞损伤的保护作用。方法培养大鼠心肌细胞H9c2,随机分为空白对照组、H/R组、Dex预处理(Dex+H/R)组、抑制剂SB203580(H/R+SB)组和Dex预处理+SB203580(Dex+H/R+SB)组。采用噻唑蓝(MTT)法检测各组细胞活力,流式细胞仪检测细胞凋亡率,试剂盒检测细胞培养液中乳酸脱氢酶(LDH)和肌酸激酶(CK)含量,分光光度计检测超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)含量,Western印迹检测细胞中磷酸化(p)-p38MAPK、细胞色素(Cyt)C和活化的含半胱氨酸的天冬氨酸蛋白水解酶(酶切Caspase)-3蛋白水平。结果与H/R组比,Dex预处理可提高H9c2细胞活力,降低细胞凋亡率,下调LDH和CK的漏出量,减少MDA含量,上调SOD和GSH-Px活性,抑制p-p38MAPK、CytC和酶切Caspase-3蛋白表达,差异有统计学意义(P0.05)。p38MAPK信号通路抑制剂SB203580可明显增强Dex对H/R心肌细胞损伤的保护作用。结论 Dex可能通过p38MAPK信号通路抑制细胞中的氧化应激,下调CytC和酶切Caspase-3蛋白的表达,抑制H9c2细胞凋亡对H/R心肌细胞损伤的保护作用。     

下调CopineⅠ抑制缺氧/复氧诱导的H9c2细胞凋亡

目的 研究Copine Ⅰ（CPNE1）对缺氧/复氧（Hypoxia/Reoxygenation,H/R）诱导H9c2细胞凋亡的作用及可能的机制。 方法 以H9c2心肌细胞为研究对象,建立H/R模型,细胞被随机分为对照组（CON）、H/R组、阴性对照（NC）+H/R和CPNE1 siRNA+H/R组,阻断实验用NF-κB的阻断剂PDTC（10 μmol/L）预处理细胞30 min。RT-PCR和Western blot方法用于检测CPNE1表达水平。细胞乳酸脱氢酶（LDH）活性采用ELISA方法检测。细胞经Annexin-V/PI染色后用流式细胞仪检测凋亡率,Western blot方法检测claved-caspase3（c-caspase3）、Bcl-2和Bax的蛋白表达水平。细胞中NF-κB活性采用ELISA方法检测。 结果 与CON组相比,H/R组CPNE1表达水平上调、LDH活性升高、凋亡率上升、c-caspase3和Bax蛋白表达升高、Bcl-2蛋白表达水平下降。与NC+H/R组相比,CPNE1 siRNA+H/R组细胞的LDH活性下降、凋亡率降低、c-caspase3和Bax蛋白表达减少、Bcl-2表达增多。此外,沉默CPNE1细胞核中NF-κB活性增强且蛋白表达上升,PDTC可逆转CPNE1 siRNA对细胞凋亡的抑制作用。 结论 下调CPNE1的表达能够抑制H/R诱导的H9c2细胞凋亡,其可能机制是通过增强NF-κB活性发挥心肌保护作用。     

京尼平通过miR-499调节缺血缺氧诱导心肌细胞线粒体途径凋亡

目的研究京尼平对缺血缺氧诱导心肌细胞线粒体途径凋亡的调节作用及其分子机制。方法培养H9c2细胞并进行分组处理,对照组用不含药物的DMEM在常氧条件下培养,缺氧组用不含药物的DMEM在缺氧条件下培养,低、中、高剂量京尼平组在缺氧条件下分别用含有2.5μmol/L、5.0μmol/L、10.0μmol/L京尼平的DMEM处理,NC抑制物组在常氧条件下转染NC抑制物,NC抑制物+缺氧组在缺氧条件下转染NC抑制物,NC抑制物+缺氧+京尼平组在缺氧条件下转染NC抑制物并用含有10.0μmol/L京尼平的DMEM处理,miR-499抑制物+缺氧+京尼平组在缺氧条件下转染miR-499抑制物并用含有10.0μmol/L京尼平的DMEM处理。比较组间心肌酶含量、细胞凋亡率、凋亡基因及miR-499表达的差异。结果京尼平组能够以剂量依赖性的方式降低细胞培养基中乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)、磷酸肌酸激酶同工酶(CK-MB)含量及细胞凋亡率和细胞中Bax、Caspase-3表达,增加细胞中Bcl-xL及miR-499的表达;转染miR-499的抑制物能够逆转10.0μmol/L京尼平降低细胞培养基中LDH、CK、CK-MB含量及细胞凋亡率、细胞中Bax、Caspase-3表达和增加细胞中Bcl-xL表达的效应。结论京尼平通过miR-499调节缺血缺氧诱导心肌细胞线粒体途径凋亡。     

牡荆苷上调FGD5-AS1抑制缺氧复氧诱导的心肌细胞氧化应激和凋亡

[目的]探究牡荆苷对缺氧复氧(H/R)诱导的心肌细胞损伤的影响及其与FGD5-AS1的调控关系。[方法]大鼠心肌细胞H9c2分为对照组,H/R组,H/R+牡荆苷低、中、高剂量组,H/R+pcDNA组,H/R+pcDNA-FGD5-AS1组,H/R+牡荆苷+si-NC组和H/R+牡荆苷+si-FGD5-AS1组。流式细胞术检测细胞凋亡,Western blot检测Caspase-3、cleaved Caspase-3蛋白表达,试剂盒检测SOD活性和MDA含量,RT-PCR检测FGD5-AS1表达。[结果]与H/R组比较,H/R+牡荆苷低、中、高剂量组凋亡率各降低13%、25%、48%,Caspase-3蛋白表达量各下降21%、38%、56%,cleaved Caspase-3蛋白表达各下降17%、40%、65%,MDA含量各下降15%、36%、52%,SOD活性升高0.88、2.73、3.86倍,FGD5-AS1表达各升高0.84、1.84、3.00倍(均P<0.05),呈浓度依赖性。与H/R+pcDNA组比较,H/R+pcDNA-FGD5-AS1组凋亡率、Caspase-3和cl...     

泛素E3连接酶TRIM10在心肌细胞缺氧/复氧损伤的作用及机制

目的:探讨泛素E3连接酶TRIM10在心肌细胞缺氧/复氧(H/R)损伤中的作用及机制。方法:培养原代的SD大鼠乳鼠心肌细胞,siRNA-TRIM10与Ad-TRIM10转染细胞48 h,再加入缺血缓冲液复制心肌细胞缺氧/复氧(H/R)模型(缺氧30 min,复氧24 h)。转染siRNA-TRIM10敲低其表达的实验分为四组:siRNA-Scramble组(转染空白对照siRNA)、siRNA-TRIM10组(转染siRNA-TRIM10)、H/R+si-Scramble组(转染siRNA-Scramble 48 h,进行H/R处理)和H/R+siRNA-TRIM10组(转染siRNA-TRIM10 48 h,进行H/R处理);转染Ad-TRIM10使其高表达分组同上(Ad-GFP作为对照)。DHE染色观察细胞氧化应激情况;TUNEL染色观察细胞凋亡情况;Western blot检测TRIM10、BAX、p-P38/P38MAPK、p-JNK/JNK及p-ERK/ERK蛋白的表达水平。结果:与Control组相比,H/R组心肌细胞中ROS的产生增加了5.8%、凋亡的发生增加了7.9%、p-JNK和p-P38MAPK蛋白的表达分别增加了21.8%和47.1%(n=5,均P<0.05),siRNA-TRIM10敲低其表达,减轻H/R处理引起的以上改变;过表达Ad-TRIM10进一步加重H/R处理引起的上述改变,与H/R组相比,过表达TRIM10+H/R组细胞ROS的产生增加了12.3%、凋亡的发生增加了15.6%、p-JNK和p-P38MAPK蛋白的表达分别增加了26.8%和25.7%(n=5,均P<0.05)。结论:E3连接酶TRIM10加重心肌细胞缺氧/复氧损伤,其机制可能通过p-JNK/p-P38MAPK途径介导。     

Brain natriuretic peptide inhibits myocardial apoptosis caused by ischemia-reperfusion injury in rats in vivo

Background This study aimed to investigate the effects of brain natriuretic peptide(BNP) on myocardial ischemiareperfusion(I/R) injury in rats in vivo.Method Twenty-one,male,Sprague-Dawley rats were randomly divided into three groups:(1) the sham operated group(SHAM) underwent thoracotomy without ligation of the coronary artery;(2) in the I /R group,the left anterior descending coronary artery was ligated for 35 min and then released to get reperfusion for 4 h;(3) in the BNP group,BNP was continuously infused 10 min after the ligation at a rate of 0.01 μg /kg /min.Then the left anterior descending coronary artery was ligated for 35 min and released to get reperfusion for 4 h.The infusion of BNP was maintained until the end of reperfusion.The myocardial infarction area in each group was determined using the 1,2,3,5-triphenyltetrazolium staining method to measure the extent of myocardial I/R injury in rats.Myocardial apoptosis was detected using the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick endlabeling(TUNEL) method.Results No myocardial infarction was observed in the SHAM group.The myocardial infarction size was 44.79 ± 7.44% in the I/R injury group and 19.72 ± 5.49% in the BNP group(P 0.01).The apoptosis indices of the SHAM,BNP,and I /R groups were 5.37 ± 4.21%,22.50 ± 9.50 %,and 45.24 ± 13.01 %,respectively(P 0.01).Conclusions BNP can decrease the myocardial infarction size caused by I/R injury in rats in vivo.This finding may be accounted for by the fact that BNP decreases myocardial apoptosis induced by I/R injury.     

Matrine inhibits bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway:An experimental study

Objective:To study the inhibitory effect of matrine on bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway. Methods:Human T24 bladder cancer cell lines were cultured and treated with different doses of matrine(0.25 mg/mL,0.5 mg/mL and 1.0 mg/mL) as well as 20 μmol/L PI3K inhibitor LY294002 for 24 h,and the cell proliferation activity,the number of invasive cells as well as the expression of p-PI3K,p-AKT,proliferation genes and invasion genes were determined. Results:Different doses of matrine could decrease the cell viability value,the number of invasive cells as well as the expression of p-PI3K,p-AKT,MMP2 and MMP9,and increase the expression of p16,p21 and p27 in dose-dependent manner; p16,p21 and p27 expression in cells of 20 μmol/L LY29002 group were significantly higher than those of 0 μmol/L LY29002 group while MMP2 and MMP9 expression were significantly lower than those of 0 μmol/L LY29002 group(P0.05). Conclusions:Matrine can inhibit bladder cancer cell proliferation and invasion in vitro and regulate the expression of cell cycle-inhibiting molecules and invasion-related genes through PI3K/AKT signaling pathway.     

GLP-1 agonist protects myocardial hypoxiareoxygenation injury through PI3K/Akt signaling pathway: an experimental study

正Objective To investigate the effects of glucagon like peptide 1(GLP-1)agonist on myocardial hypoxia reoxy-genation injury and its molecular mechanism.Methods H9C2 cells were divided into control group,hypoxia reoxygenation(H/R)group,H/R+GLP-1 group,and H/R+GLP-1+phosphatidylinositol-3-kinase(PI3K)inhibitor LY294002 group.The cell proliferation activity,apoptosis rate,enzyme contents in the medium and     

miR-200c-3p靶向XIAP调控缺氧复氧诱导的心肌细胞凋亡

目的探讨miR-200c-3p对缺氧复氧心肌细胞凋亡的影响及作用机制。方法构建缺氧复氧(H/R)H9c2细胞。运用实时荧光定量反转录聚合酶链反应(qRT-PCR)法检测细胞中miR-200c-3p、X连锁凋亡抑制蛋白(XIAP)信使核糖核酸(mRNA)的表达。将H9c2细胞分为H/R+anti-miR-NC组(转染anti-miR-NC)、H/R+anti-miR-200c-3p组(转染anti-miR-200c-3p)、H/R+pcDNA组(转染pcDNA)、H/R+pcDNA-XIAP组(转染pcDNA-XIAP)、H/R+anti-miR-200c-3p+si-NC组(共转染anti-miR-200c-3p和si-NC)、H/R+anti-miR-200c-3p+si-XIAP组(共转染anti-miR-200c-3p和si-XIAP),用脂质体法转染至H9c2细胞,再进行缺氧复氧处理。免疫印迹(Western blot)、噻唑蓝(MTT)、流式细胞术检测细胞中XIAP、半胱氨酸天冬氨酸蛋白酶(Caspase-3)、裂解的半胱氨酸天冬氨酸蛋白酶(cleaved Caspase-3)、B细胞淋巴瘤/白血病2 X蛋白(Bax)、B细胞淋巴瘤/白血病2(Bcl-2)的表达、细胞增殖、细胞凋亡;双荧光素酶报告基因检测实验检测细胞中miR-200c-3p与XIAP的结合力。结果成功构建缺氧复氧H9c2细胞;与正常培养的H9c2细胞比较,H/R组H9c2细胞中miR-200c-3p表达明显上调,XIAP表达明显下调;抑制miR-200c-3p、过表达XIAP均可抑制H/R H9c2细胞的凋亡,下调cleaved Caspase-3、Bax,上调Bcl-2;miR-200c-3p可显著抑制XIAP 3′UTR野生型报告基因活性,并负向调控XIAP的表达;敲减XIAP可逆转抑制miR-200c-3p对H/R H9c2细胞的凋亡抑制作用。结论 miR-200c-3p可诱导缺氧复氧心肌细胞的凋亡,其机制与靶向XIAP有关,可为心血管疾病的治疗提供新靶点。     

牛磺酸通过激活PI3K/Akt信号通路抑制高糖诱导的内皮细胞凋亡

目的 探讨牛磺酸对高糖诱导的内皮细胞凋亡的影响及其信号途径.方法 取健康产妇分娩后12h内的脐带分离人脐静脉内皮细胞(HUVEC),进行细胞培养并分为5组:正常葡萄糖组(5 mmol/LD-葡萄糖,NG组);高糖组(30 mmol/LD-葡萄糖,HG组);NG+TAU组(5mmol/LD-葡萄糖+5 mmol/L牛磺酸);HG+TAU组(30 mmol/L D-葡萄糖+5 mmol/L牛磺酸);HG+TAU+Wo组(30 mmol/LD-葡萄糖+5 mmol/L牛磺酸+50 nmol/L wortmannin).干预48 h后应用流式细胞术检测细胞凋亡情况,Western印迹检测磷酸化蛋白激酶B(p-Akt)蛋白的表达水平,2,7-二氯二氢荧光素二乙酯(H2DCF-DA)探针技术及荧光倒置显微镜检测活性氧簇的相对含量.结果 与NG组相比,HG组细胞的凋亡率显著增加(P＜0.05).与HG组相比,HG+TAU组的凋亡率下降(P＜0.05).与HG+TAU组相比,HG+TAU+Wo组的凋亡率较高(P＜0.05).与NG组相比,HG组磷酸化-Akt蛋白表达下降(P＜0.05).与HG组比较,HG+TAU组磷酸化-Akt蛋白表达增加(P＜0.05).与HG+TAU组相比,HG+TAU+Wo组磷酸化-Akt蛋白表达下降(P＜0.05).牛磺酸可降低高糖诱导的活性氧簇生成(P＜0.05),这一作用亦可被wortmannine所阻断(P＜0.05).结论 牛磺酸通过PI3K/Akt信号途径调节细胞内活性氧簇生成,进而在高糖环境下发挥其抗凋亡作用.     

高原环境中妊娠期母体缺氧对胎羊心肌组织影响的实验研究

目的 观察高原环境中妊娠期母体绵羊不同程度的缺氧造成胎羊心肌组织及线粒体结构和功能的改变。方法 选取 24 只平原环境生长的妊娠期绵羊,随机分为平原对照组（LAC）,轻度低氧暴露组（MHE）和重度低氧暴露组（SHE）,应用人工实验舱,通过调整各项参数,精确模拟高原低氧的气候环境,制作不同程度缺氧的妊娠期动物模型。实验结束后,解剖胎羊,对胎羊及其重要内脏器官称重。获取各组胎羊心肌组织进行病理切片,用苏木素-伊红（HE）染色法、扫描电子显微镜及透射电子显微镜技术检测观察胎羊心肌组织和线粒体的病理改变情况。结果 和LAC组相比,MHE组和 SHE 组胎羊体重均明显降低（P<0.05）;和 LAC 组或 MHE 组相比,SHE 组胎羊心脏绝对重量明显降低（P<0.05）,而心脏相对重量未见明显差异性改变（P>0.05）。心肌组织样本HE 染色、扫描电子显微镜及透射电子显微镜显示,MHE 组、 SHE 组和 LAC 组相比,胎羊的心肌组织出现了不同程度的损伤,线粒体的数量、大小、形态结构及分布发生不同程度的异常,其中以 SHE 组心肌和线粒体异常和损伤最为显著。结论 高原缺氧环境能对胎儿心肌组织及线粒体造成损伤,同时随着海拔高度的升高,心肌及线粒体的损伤程度逐渐加重,提示在高原缺氧状态下,心肌损伤程度和线粒体数量、大小、形态和分布具有相关性。     

培养心肌细胞缺氧复氧性损伤机制及ICAM-1 MAb的干预研究

目的 :探讨缺氧复氧性损伤的发生机制 ,澄清IL 1在损伤中的作用及ICAM 1MAb对损伤的影响。方法 :新生Wistar大鼠 5 0只 ,取其心肌细胞和主动脉内皮细胞培养 ,分离其外周血中性粒细胞 ,分设正常条件培养组 ,单纯缺氧复氧组 (HR) ,正常培养 +IL 1β(10 0u ml)刺激组 ,将以上 3组再分别分为 :不干预组和ICAM 1MAb(10 0ng ml)干预组 ;于缺氧 1h复氧 6h ,测定心肌细胞一氧化氮合酶 (NOS) ,细胞胞浆游离钙 ([Ca2 + ]i) ,超氧化物歧化酶 (SOD) ,丙二醛 (MDA) ,还原型谷胱苷肽 (GSH)和中性粒细胞与内皮细胞粘附率。结果 :心肌细胞缺氧复氧时 ,[Ca2 + ]i、MDA显著增加 ,而SOD、GSH、NOS明显下降 ;IL 1β、ICAM 1蛋白质表达 ,中性粒细胞与内皮细胞的粘附率显著增加。IL 1干预刺激组的上述指标变化类似于缺氧复氧组。ICAM 1MAb可明显改善SOD、GSH及NOS下降的程度和MDA增高的程度 ,降低中性粒细胞与内皮细胞的粘附率 ,但不能改善 [Ca2 + ]i超载和IL 1β的表达水平 ,P >0 0 5。 结论 :IL 1β通过直接或激活ICAM 1导致中性粒细胞与内皮细胞的粘附增加而引起细胞损伤 ,但钙超载 ,氧自由基和NO NOS系统也共同参与了缺氧复氧性损伤。ICAM 1MAb通过抑制中性粒细胞系统、减轻氧自由基产生、改善NOS代谢可部分减轻损伤。     

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.     

黄芪注射液抑制缺氧缺糖后复氧复糖大鼠海马神经细胞凋亡的研究

目的 观察黄芪注射液对缺氧缺糖后复氧复糖大鼠海马神经细胞凋亡的抑制作用.方法 取体外原代培养8 d的正常乳鼠海马神经细胞,缺氧缺糖0.5 h后正常培养,并用黄芪注射液进行干预. MTT法测定细胞活性,光学显微镜下观察细胞形态,Annexin V-FITC/PI双染法流式细胞术检测凋亡细胞百分率.结果 与正常对照组比较,缺氧缺糖后复氧复糖组(模型组)在复氧复糖后各个时间点海马神经细胞的活性明显下降(P＜0.05),其中复氧复糖后6 h海马神经元活性最低,与其他时间点比较差异显著(P＜0.05). 各时间点黄芪注射液低浓度组和高浓度组的细胞活性与同时间点模型组相比无显著性差异(P＞0.05)黄芪注射液中浓度组各时间点的细胞活性明显增高(P＜0.05).模型组各时间点细胞凋亡率较正常对照组明显升高(P＜0.05),黄芪注射液组各时间点细胞凋亡率较模型组组明显下降 (P＜0.05).光镜下观察模型组可见大量凋亡细胞,细胞核皱缩、碎裂,核深染并可见凋亡小体;坏死细胞肿胀,细胞膜连续性破坏;黄芪注射液组凋亡细胞明显减少且以细胞核皱缩为主,细胞坏死程度较模型组明显减轻.结论 黄芪注射液可以抑制缺氧缺糖后复氧复糖大鼠海马神经细胞的凋亡,提高细胞的活性,对缺氧缺糖后复氧复糖大鼠海马神经细胞有保护作用.     

miR-376b-3p通过靶向FGF21加重缺氧复氧心肌细胞的损伤

目的 探讨miR-376b-3p对缺氧复氧(H/R)心肌细胞增殖、凋亡的影响及机制。方法 培养心肌细胞H9c2,缺氧复氧法体外模拟H/R细胞损伤,建立心肌细胞损伤模型。用流式细胞术、免疫印迹(Western blot)、酶联免疫吸附(ELISA)检测正常对照组、H/R组、anti-miR-NC组、anti-miR-376b-3p组、anti-miR-376b-3p+si-NC组、anti-miR-376b-3p+si-成纤维细胞生长因子21(FGF21)组细胞凋亡率、凋亡相关蛋白B淋巴细胞瘤2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)表达和肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素17(IL-17)情况。双荧光素酶报告基因实验检测细胞的荧光活性。结果 成功建立缺氧复氧损伤的细胞模型;模型组细胞中miR-376b-3p表达显著升高,FGF21表达显著降低,并且抑制miR-376b-3p可以减轻损伤细胞的凋亡和TNF-α、IL-6、IL-17的含量,以及上调Bcl-2,下调Bax。此外,miR-376b-3p还可靶向FGF21 mRNA。抑制FGF21后,抑制miR-376b-3p对缺氧复氧损伤的H9c2细胞的保护作用被减弱。结论 miR-376b-3p可促进缺氧复氧心肌细胞的凋亡和炎性反应,其机制与靶向FGF21 mRNA相关。     

An experimental infection caused by the Issyk-Kul arbovirus]

Pathogenic properties of Issyk-Kul virus have been experimentally studied in green monkeys, golden hamsters and white mice. The virus was identified in the blood and organs of all the animals. Pathohistological studies have revealed inflammatory and dystrophic changes in the central nervous system, lungs, liver and kidneys. Pronounced immunomorphological changes have been observed in the spleen. The virus possessed pantropic properties and caused generalized infection in all the animals irrespective of the mode of infection. In monkeys asymptomatic infection was accompanied by marked organ damages and virusemia. The presence of specific antibodies in the blood indicated a low efficacy of humoral immunity in this infection.     

Propofol inhibits hypoxia/reoxygenation-induced human gastric epithelial cell injury by suppressing the Toll-like receptor 4 pathway

This study aimed to investigate the role of the Toll-like receptor 4 (TLR4) pathway in normal human gastric epithelial (GES-1) cells under hypoxia/reoxygenation (H/R) in vitro, and the effect of propofol on injured GES-1 cells as well as its possible mechanism. Before H/R induction, GES-1 cells were preconditioned with fat emulsion, propofol, or epigallocatechin gallate. Then cell viability, cell apoptosis, and related molecules in the cells were analyzed under experimental conditions. We found that propofol 50 μmol/L markedly inhibited the H/R injury under hypoxia 1.5 h/reoxygenation 2 hours by promoting GES-1 cell viability and decreasing cell apoptosis. The TLR4 signal may be involved in the protective effect of propofol against H/R injury. The malondialdehyde contents and superoxide dismutase activities were recovered under propofol preconditioning. In summary, propofol preconditioning may exert a protective effect on H/R injury in GES-1 cells and the mechanism may be via inhibition of the activated TLR4 signal under H/R conditions.     

Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway

Thrombospondin-1 (TSP1) is a potent natural inhibitor of angiogenesis. Although TSP1 has been reported to induce endothelial cell apoptosis in vitro and to downregulate neovascularization in vivo, the molecular mechanisms that link these two processes have yet to be established. Here we report that TSP1 mediates endothelial cell apoptosis and inhibits angiogenesis in association with increased expression of Bax, decreased expression of Bcl-2, and processing of caspase-3 into smaller proapoptotic forms. The ability of TSP1 to induce both endothelial cell apoptosis in vitro and to suppress angiogenesis in vivo was blocked by the caspase-3 inhibitor z-DEVD-FMK. TSP1 also attenuated VEGF-mediated Bcl-2 expression in endothelial cells in vitro and angiogenesis in vivo. Furthermore, TSP1 induced endothelial cell apoptosis and inhibited neovascularization in sponge implants in SCID mice. We conclude that TSP1 induces endothelial cell apoptosis and inhibits neovascularization by altering the profile of survival gene expression and activating caspase-3.