补骨脂酚通过抑制凋亡、氧化应激和炎症反应缓解小鼠脓毒症脑病

目的:探究补骨脂酚能否抵抗小鼠脓毒症脑病。方法:通过小鼠盲肠结扎穿孔法建立脓毒症脑损伤模型。盲肠结扎穿孔后通过腹腔注射补骨脂酚(10 mg/kg)。小鼠随机分为以下4组:假手术(Sham)组;单纯补骨脂酚处理(BAK)组;盲肠结扎穿孔(CLP)组;盲肠结扎穿孔+补骨脂酚处理(CLP+BAK)组。盲肠结扎穿孔48小时后检测脑组织水含量、血脑屏障通透性、凋亡率、IL-1β与TNF-α表达量、MDA含量、SOD与CAT活性。结果:与Sham组相比,CLP组小鼠脑组织水含量(增加21.20%)、脑组织Evans蓝含量(增加237.05%)、凋亡率、MDA含量、IL-1β与TNF-α表达量均明显增高,而SOD与CAT活性明显降低(P0.05)。与CLP组相比,补骨脂酚处理可明显降低脑组织水含量(下降10.94%)、Evans蓝含量(下降39.40%)、凋亡率、MDA含量、IL-1β与TNF-α表达量,而增加SOD与CAT活性(P 0.05)。结论:补骨脂酚通过抑制凋亡、氧化应激和炎症反应,最终减轻脓毒症脑损伤。     

富氢液对大鼠脓毒血症引起急性肺损伤的影响

目的:探讨富氢液对大鼠脓毒血症引起急性肺损伤的影响。方法:24只大鼠建立盲肠结扎穿孔法(CLP)脓毒症模型,随机均分为以下3组(n=8):假手术组(Sham组)、CLP组及CLP+富氢液组。CLP+富氢液组于CLP后即时、6及18 h腹腔分别注射富氢液5 ml/kg,CLP组及假手术组于上述相应时间点腹腔注射富氢液5 ml/kg。CLP或假手术24 h后检测肺组织TNF-α、IL-6、HMGB1、IL-10、MDA、SOD、MPO活性及干湿重比(W/D)并采用HE染色法进行肺组织学评分。结果:与Sham组比较,CLP组及CLP+富氢液组肺组织TNF-α、IL-6、HMGB1、IL-10、MDA、SOD、MPO活性、W/D及肺组织学评分明显升高而SOD活性明显降低(P<0.05);与CLP组相比,CLP+富氢液组IL-6、HMGB1、MDA、MPO明显降低及肺组织学评分明显降低而SOD明显升高(P<0.05)。结论:富氢液降低脓毒血症的炎性反应和氧化应激,从而改善ALI时的肺功能。     

饱和氢气生理盐水对盲肠结扎穿孔大鼠肺损伤的干预作用*

目的: 观察饱和氢气生理盐水对盲肠结扎穿孔(CLP)大鼠肺组织的作用。方法: 将24只健康雄性SD大鼠(体重250~300 g)随机分成4组(每组6只):①假手术对照组(Sham组)+生理盐水组:盲肠根部穿过丝线,不行结扎和穿孔,手术前10 min腹腔注射生理盐水(10 mg/kg);②CLP组+生理盐水组:结扎盲肠根部并用18号针头穿刺2个孔,2个孔相距约1cm,手术前10 min腹腔注射生理盐水(10 mg/kg);③Sham+H₂组:手术前10 min腹腔注射饱和氢气生理盐水(10 mg/kg); ④CLP+ H₂组:手术前腹腔注射饱和氢气生理盐水(10 mg/kg)。各组于手术后8 h进行观察:采用生物化学和RT-PCR的方法分别检测大鼠肺组织中CSE/H₂S体系的变化。采用H₂S供体硫氢化钠(NaHS)诱导的肺组织损伤动物模型,另取32只健康雄性SD大鼠(体重250~300 g),随机分为4组(每组8只):①生理盐水组:腹腔注射生理盐水(10 mg/kg);②H₂S组:腹腔注射H₂S供体NaHS(56 μmol/kg);③H₂S+H₂组:腹腔注射NaHS前10 min注射饱和氢气生理盐水(10 mg/kg);④H₂组:腹腔注射生理盐水前10 min注射饱和氢气生理盐水(10 mg/kg)。于给药后8 h测定肺系数,检测肺组织中MDA含量、MPO活性及细胞因子TNF-α、IL-6和IL-10含量,观察肺组织形态学变化。结果: 饱和氢气生理盐水可抑制CLP大鼠肺组织中CSE/H₂S体系:减少CLP大鼠肺组织中H₂S的生成,抑制H₂S的合成酶CSE的活性及mRNA表达 (P均＜0.05);外源性给予H₂S(NaHS)可造成肺组织损伤,饱和氢气生理盐水可明显减轻H₂S所致的肺组织损伤:大鼠肺系数明显减小(P＜ 0.05),MDA含量下降(P＜0.05);肺组织MPO活性下降(P＜0.05);大鼠肺间质和肺泡中PMN的浸润程度明显减轻,肺组织形态及IQA接近正常(P＜0.05)。结论: 饱和氢气生理盐水可通过抑制CLP大鼠肺组织中CSE/H₂S体系,发挥其改善CLP大鼠肺组织损伤的作用。     

蕨麻多糖对小鼠脾淋巴细胞上清液IFN-γ和可溶性LAG-3分子水平的影响

为了观察蕨麻多糖对急性低剂量镉染毒小鼠脾淋巴细胞上清液中IFN-γ和可溶性LAG-3(soluble LAG-3,s LAG-3)分子水平的影响。将试验小鼠一次性腹腔注射氯化镉溶液(1 mg/kg)染毒,观察24h即造模成功后,腹腔注射低、中、高剂量蕨麻多糖治疗一周,于实验终末测各组小鼠脾脏、胸腺指数,ELISA法测IFN-γ、s LAG-3含量;免疫荧光法观察CD3+、CD4+、CD8+T淋巴细胞。结果表明蕨麻多糖低、中、高剂量组中,IFN-γ、s LAG-3的含量较空白对照组和单纯镉染阳性对照组均增高,以高浓度组增高明显(P0.05);CD3+、CD4+T淋巴细胞较空白对照组和单纯镉染阳性对照组均增多,仍以高浓度组增多明显,CD8+T变化不显著。蕨麻多糖能促进急性低剂量镉染毒小鼠脾淋巴细胞分泌IFN-γ和s LAG-3,CD3+、CD4+T淋巴细胞亦相应增加。     

黄精多糖对力竭运动小鼠胸腺胸腺指数、脾脏指数、T淋巴细胞亚群、巨噬细胞吞噬功能的影响

为了探讨黄精多糖对力竭训练后小鼠胸腺指数、脾脏指数、T淋巴细胞亚群、巨噬细胞功能的影响,本研究以100昆明雄性小鼠,随机分为安静对照组、运动训练组、运动垣低剂量给药组、运动垣中剂量给药组、运动垣高剂量给药组,每组20只,在实验结束前3 d后,每组小鼠随机分为M、N两个组,M组用于胸腺指数、脾脏指数、T淋巴细胞亚群的测试,N组用于巨噬细胞功能的测定。除安静对照组外,其余各组小鼠进行为期20 d,隔天一次的无负重力竭游泳训练,三个给药组小鼠同时按50 g/kg·d、100 g/kg·d、150 g/kg·d三种剂量灌胃。测定各组小鼠胸腺指数、脾脏指数、T淋巴细胞亚群、巨噬细胞功能。结果表明运动后小鼠胸腺指数、脾脏指数、CD3+、CD4+、CD4+/CD8+、巨噬细胞吞噬率、吞噬指数明显下降。运动垣中剂量给药组、运动+高剂量给药组胸腺指数、脾脏指数、CD+3、CD+4、CD+4/CD+8、巨噬细胞吞噬率、吞噬指数显著或及显著高于运动训练组,运动垣低剂量给药组CD+3、CD+4、CD+4/CD+8显著高于运动训练组。运动运动垣高剂量给药组腺指数、脾脏指数、CD++3、CD+4、CD+4/CD8、巨噬细胞吞噬率、吞噬指数显著高于运动垣低剂量给药组。研究提示,黄精多糖可提高长期力竭训练小鼠的免疫能力,具有显著免疫增强效应,其中以高剂量黄精多糖免疫效果最佳。本研究为黄精多糖在运动免疫领域的应用提供新思路。     

维生素E对TCDD染毒小鼠白细胞介素和T细胞亚群的影响

为研究维生素E(VE)对2,3,7,8四-氯代二苯并-对-二噁英(TCDD)染毒雄性小鼠白细胞介素(IL)和T细胞亚群的影响,我们设计了5个实验组,将40只小鼠随机分为5组,5组动物给予TCDD和维生素E的水平依次为:TCDD 0 ng/kg和VE0 mg/kg、TCDD 100 ng/kg和VE0 mg/kg、TCDD 100 ng/kg和VE20 mg/kg、TCDD 100ng/kg和VE100 mg/kg、TCDD 100 ng/kg和VE500 mg/kg。灌胃7周后取其血液和脾脏,用酶联免疫法测小鼠血清IL的水平,用流式细胞仪法测定脾脏T淋巴细胞亚群的变化。结果表明:TCDD染毒组小鼠血清IL-1α水平明显高于对照组;VE20 mg/kg和100 mg/kg的两组,其血清IL-1α水平均明显低于染毒组;而VE500 mg/kg组,其血清IL-1α水平与染毒组间差异没有统计学意义;TCDD染毒组小鼠血清IL-2水平明显低于对照组;VE100 mg/kg和500 mg/kg两组,其血清IL-2水平明显高于染毒组;TCDD染毒组CD4 T淋巴细胞百分比明显低于对照组;给予VE的三组,其脾CD4 T淋巴细胞百分比与TCDD染毒组相比有升高的趋势,但没有统计学意义;TCDD染毒组小鼠脾CD8 T淋巴细胞百分比明显高于对照组;VE为100 mg/kg组,其脾CD8 T淋巴细胞百分比明显低于染毒组和VE20 mg/kg两组;VE500 mg/kg组,其脾CD8 T淋巴细胞百分比明显低于染毒组。表明TCDD能导致机体白细胞介素分泌的紊乱以及脾脏T淋巴细胞亚群的变化,而适当剂量的VE对TCDD所致的毒性有拮抗作用。     

和厚朴酚通过激活SIRT1/FOXO1信号通路抵抗小鼠脓毒症脑损伤

目的:探究和厚朴酚是否通过激活SIRT1/FOXO1信号通路抵抗小鼠脓毒症脑损伤。方法:通过C57BL/6小鼠盲肠结扎穿孔法建立脓毒症脑损伤模型。小鼠随机分为以下6组:假手术(Sham)组;和厚朴酚处理(HKL)组;盲肠结扎穿孔(CLP)组;盲肠结扎穿孔+和厚朴酚处理(CLP+HKL)组;EX527 (SIRT1特异性抑制剂)预处理+盲肠结扎穿孔+和厚朴酚处理(CLP+HKL+EX527)组;EX527预处理+盲肠结扎穿孔(CLP+EX527)组。盲肠结扎穿孔48 h后检测脑组织内水含量、凋亡率及凋亡相关蛋白Bax、Bcl-2和cleaved Caspase-3的表达情况、炎症相关分子IL-1β与TNF-α、SIRT1信号通路相关蛋白表达情况。结果:与CLP组相比,CLP+HKL组脑组织内SIRT1的表达量及活性、Bcl-2表达量明显增加,而脑组织水含量、凋亡率、Bax、cleaved Caspase-3、IL-1β与TNF-α的表达量明显降低(均P 0.05)。EX527可明显抑制HKL的上述脑保护作用(P 0.05)。结论:和厚朴酚主要通过激活SIRT1/FOXO1信号通路,抑制凋亡与炎症,从而缓解脓毒症脑损伤。     

人脐带间充质干细胞移植对脓毒症小鼠的保护作用研究

为了评价人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,h UCMSCs)移植对脓毒症小鼠的疗效,作者将90只小鼠随机均分为3组:假手术(Sham)组、PBS治疗组和h UC-MSCs治疗组。治疗组小鼠采用盲肠结扎穿孔(cecal ligation and puncture,CLP)方式建立脓毒症模型;假手术组小鼠仅开腹探查盲肠,不行CLP。Sham组和PBS治疗组术后3h经尾静脉注射0.2mL PBS,hUC-MSCs治疗组注射等体积的h UC-MSCs悬液(含细胞7.5×10~5/mL)。术后24 h,流式细胞术检测各组小鼠外周血及腹腔灌洗液(peritoneal lavage fl uid,PLF)中的中性粒细胞数量,ELISA检测血清炎症因子水平,生化检验评价肝肾功,HE(hematoxylin and eosin)染色评估肝、肾、肺组织病理变化。观察术后小鼠一般情况,绘制120 h生存曲线。结果显示,hUC-MSCs可以显著改善脓毒症小鼠一般状况,减少中性粒细胞浸润,降低小鼠体内炎症水平,改善器官功能,减轻组织器官损伤,显著提高小鼠存活率。该研究显示了人脐带间充质干细胞移植对脓毒症小鼠的良好保护作用。     

荷瘤小鼠脾脏功能紊乱型CD8~+T细胞数量的分析研究

目的分析荷瘤小鼠与正常小鼠脾脏功能紊乱型CD8~+T细胞(Tim-3~+/PD-1~+ CD8~+T细胞)的数量比例,预测肿瘤患者功能紊乱型CD8~+T细胞的情况,为改善肿瘤的免疫治疗提供参考。方法设置荷瘤小鼠组与正常小鼠组,每组各3只,分别从两组小鼠脾脏中提取分离获得CD8~+T细胞,用FITC标记的PD-1抗体、PE标记的Tim-3抗体与CD8~+T细胞共孵育,孵育后经流式细胞术检测获得数据,并分析结果。结果正常小鼠组脾脏CD8~+T细胞占脾脏T淋巴细胞总数百分比为7.7%,荷瘤小鼠组脾脏CD8~+T细胞占脾脏T淋巴细胞总数百分比为1.2%,两组的CD8~+T细胞数量有明显差异性(χ~2=0.299,P=0.02);正常小鼠组脾脏功能紊乱型CD8~+T细胞占CD8~+T细胞总数的百分比为1.17%,荷瘤小鼠组脾脏功能紊乱型CD8~+T细胞占CD8~+T细胞总数的百分比为1.17%,两组数据差异无统计学意义(χ~2=0.00,P=1.00)。结论荷瘤小鼠与正常小鼠脾脏组织中功能紊乱型CD8~+T细胞的数目无明显差异。     

枸杞多糖调控口蹄疫重组腺病毒疫苗诱导DC及T细胞亚群的研究

近年来,随着许多病毒性疾病的发展,社会对于新型疫苗的研发迫在眉睫。与传统疫苗相比,新型疫苗具有安全可靠的优点,但其免疫原性较弱的特点也十分突出,因此,研究出安全稳定有效的免疫调节剂来增强疫苗的免疫效果成为研究学者们共同的关注点。枸杞是传统的名贵补益中药,枸杞多糖(Lycium barbarum polysaccharide,LBP)是其中的主要生物活性成分,具有免疫调节、抗肿瘤、抗衰老等多种生物学作用。本研究通过体内实验观察LBP对口蹄疫重组腺病毒疫苗(rAd5VP1)诱导小鼠脾脏树突状细胞(Dendritic cells,DC)成熟、辅助性T细胞1(T helper cells 1,Th1)、辅助性T细胞2(T helper cells 2,Th2)、滤泡辅助性T细胞(T follicular helper cells,Tfh)及调节性T细胞(Regulatory T cells,Treg)分化的免疫调节作用,为阐明LBP免疫调节的新机制提供实验依据。6周龄的雌性BALB/c小鼠随机分为5组,每组5只,所有小鼠均行腹腔注射rAd5VP1,同时分别给予低剂量(10mg/kg·d)、中剂量(20mg/kg·d)、高剂量(40mg/kg·d)的LBP,阴性对照组和阳性对照组分别给予磷酸盐缓冲液(Phosphate buffer solution,PBS)和脂多糖(Lipopolysaccharide,LPS)(1mg/kg·d)。免疫7d后,应用流式细胞术(Flow cytometry,FCM)检测小鼠脾脏DC(CD11c+MHCⅡ+CD86+)、Th1细胞(CD4+IFN-γ+)、Th2细胞(CD4+IL-4+)、Tfh细胞(CD4+CXCR5+)及Treg细胞(CD4+CD25+FoxP3+)的数量与比例。结果表明,与PBS组相比,LBP能明显诱导DC的成熟,DC表面的共刺激分子CD86的表达量明显升高;LBP能明显促进Th2细胞、Tfh细胞的分化,LBP对Th1细胞的分化无明显影响,LBP能抑制Treg细胞的分化。本研究证实LBP作为疫苗免疫调节剂,可调控DC及Th细胞亚群的分化而发挥免疫调节作用,为LBP的免疫调节机制提供理论依据。     

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.     

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     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

鸡传染性法氏囊病病毒研究进展

传染性法氏囊病(Infection bursal disease, IBD)是由鸡传染性法氏囊病毒(Infectious bursal disease virus, IBDV)引起的鸡和火鸡的一种高度接触性传染病,给世界各国的禽养殖业带来了巨大损失.自IBDV发现至今新的变异株不断出现,分子结构的改变导致病毒致病力的改变及宿主对疫苗应答的改变,使得传统的疫苗已不能控制其流行,因此各国学者对其基因组结构和功能进行了广泛深入的研究,并积极研制新型有效的疫苗以达到防治的目的.     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).