In vitro antiviral activity of dehydroepiandrosterone and its synthetic derivatives against vesicular stomatitis virus

In this work the antiviral activity of 20 dehydroepiandrosterone (DHEA) analogs with different substituents at positions C-3, C-15, C-16 and C-17 were evaluated against vesicular stomatitis virus (VSV) in Vero cell cultures. The selectivity indexes (SI) obtained with DHEA and epiandrosterone (EA) were 50 and 72.6, respectively. The work showed that the compounds 21-norpregna-5,17(20)-dien-3β,16α-diyl-diacetate, 17,17-ethylendioxyandrostan-5,15-dien-3β-ol and 3β-hydroxypregn-17(20)-en-16-one had higher SI values than ribavirin, which was used as a reference drug. The antiviral mode of action of DHEA was also investigated against VSV replication in Vero cells, and time of addition experiments showed that DHEA mainly affected a late event in the virus growth cycle. Analysis of RNA and protein synthesis indicated that DHEA adversely affected positive strand RNA synthesis and viral mature particle formation.     

脱氢表雄酮对AA肉种鸡生产性能和肌纤维发育的影响

为探讨母源性添加DHEA对子生理机能影响的母体效应机制,本试验选用100羽16周龄AA种母鸡随机分成对照组、低剂量试验组、中剂量试验组和高剂量试验组,每组25只。于34周龄开始在饲料中添加DHEA,剂量分别为0、25、50和100 mg.kg-1,连续饲喂7周,期间记录每天的产蛋数并称重。在试验的第49天禁饲12 h,宰杀各组鸡。采集血液、腹脂、左侧胸肌和腿肌,计算产蛋率、平均蛋重、腹脂率、相对胸肌重和相对腿肌重。测定血清中尿酸(UA)和肌酐(Cr)含量。取腿肌和胸肌制作冰冻组织切片,测定肌纤维直径和密度。结果表明,与对照组相比,低剂量组母鸡产蛋率极显著升高(P0.01),中剂量组和高剂量组则极显著降低(P0.01);试验组平均蛋重差异不显著(P0.05);高剂量组母鸡的相对腿肌重显著升高(P0.05),而低剂量组和中剂量组差异不显著(P0.05);试验组腹脂率和相对胸肌重量差异不显著(P0.05);低剂量组血清UA含量极显著升高(P0.01),中剂量组有升高趋势,高剂量组显著升高(P0.05);中剂量组和高剂量组血清Cr含量没有显著变化(P0.05),低剂量组极显著升高(P0.01);3个剂量组AA肉种鸡胸肌肌纤维直径和密度均没有显著变化(P0.05);低剂量组腿肌肌纤维直径没有显著变化(P0.05),中剂量组显著减小(P0.05),高剂量组极显著减小(P0.01);低剂量组腿肌肌纤维密度没有显著变化(P0.05),中剂量组显著增大(P0.05),高剂量组极显著增大(P0.01)。     

动物源性激素DHEA对拟南芥植株根系生长发育的影响

用DHEA处理拟南芥种子,观察经DHEA处理后拟南芥幼苗根系的生长状态,并研究其体内氧化还原状态的变化。结果表明:经DHEA处理后,拟南芥幼苗的主根缩短了20%,葡萄糖-6-磷酸脱氢酶(G6PD)酶活降低,过氧化氢(H2O2)、丙二醛(MDA)及还原性谷胱甘肽(GSH)含量升高,抗氧化酶总超氧化物歧化酶(T-SOD)和过氧化物酶(POD)活力均增强,但过氧化氢酶(CAT)活力下降。说明动物源性激素DHEA在植物中通过抑制G6PD的酶活,导致植株内的氧化还原状态发生变化,从而影响了主根的生长能力。     

脱氢表雄酮对阉公猪脂类代谢的影响

以阉公猪为试验对象,探讨日粮中添加脱氢表雄酮（DHEA）对阉公猪脂类代谢和脂肪沉积的影响。将45头体质量40kg左右的杜×（长×大）三元杂交阉公猪随机分成3组,即对照组（基础日粮）、试验Ⅰ组（基础日粮＋25mg/kg DHEA）和试验Ⅱ组（基础日粮＋75mg/kg DHEA）,饲喂105d后,从每组选出体质量相近的6头猪屠宰,记录内脏器官和脂肪组织质量,同时采集血液和组织样品。结果显示：不同质量浓度（25,75mg/kg）的DHEA处理对阉公猪的采食量、日增质量及料重比无显著影响（P〉0.05）;但显著降低了阉公猪背膘厚（P〈0.05）、肾周脂肪指数（P〈0.05）及肠系膜脂肪指数（P〈0.05）,而对肌内脂肪含量无显著影响;同时还可显著降低血清总胆固醇、甘油三酯、非酯化脂肪酸浓度（P〈0.05）,而对血清低密度脂蛋白胆固醇（LDL-C）及血糖含量影响不显著（P〉0.05）,并发现75mg/kg DHEA处理可显著增加血清高密度脂蛋白胆固醇（HDL-C）含量（P〈0.05）;还能显著增加血清DHEA浓度,但对血清DHEA-S和胰高血糖素浓度没有显著影响,且75mg/kg DHEA处理还能够显著降低血清皮质醇浓度（P〈0.05）和血清胰岛素浓度（P〈0.05）。提示：日粮添加DHEA可调控阉公猪的脂类代谢,降低脂肪沉积。     

脱氢表雄酮诱导大鼠多囊卵巢综合征的研究

探索用脱氢表雄酮(dehydroepiandrosterone,DHEA)诱导雌性大鼠建立多囊卵巢综合征(Polycystic ovary syndrome,PCOS)模型的方法.采用性成熟雌性SD大鼠20只,随机分为两组,其中试验组10只,腹腔注射DHEA 6 mg/100(g·d-1);对照组10只同时注射生理盐水.试验中每天用阴道涂片法进行发情鉴定,31 d后分剐称取大鼠的卵巢、子宫、肝脏、肾和脾的重量,并对卵巢做石蜡切片观察.结果表明试验组大鼠的发情周期严重紊乱,卵巢呈多囊样病变,而对照组正常;对照组和试验组在肝重上差异极显著,且卵巢出现了异常的多卵母细胞卵泡现象.     

Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus

Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals (P < 0.05), and F(-)F(+) cats had significantly lower plasma values than monoinfected cats (P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV(+) females had higher DHEA concentrations than the corresponding males (P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression.     

母源性脱氢表雄酮对子代艾维因肉鸡脂肪代谢及肌肉品质的影响

本文以AA肉鸡为试验对象,研究母源性添加脱氢表雄酮(DHEA)对子代艾维因肉鸡脂肪代谢和肌肉品质的影响。将34周龄AA肉种鸡随机分为对照组(Con)、添加25 mg.kg-1DHEA的低剂量组(L)和50 mg.kg-1DHEA的高剂量组(H),2周后从各组收集种蛋进行孵化,随机选取180只出壳后的子代鸡,根据其母代饲料中添加DHEA的情况相应的分为对照组、低剂量组、高剂量组。饲喂至21 d宰杀,采集血清、肝脏、腹脂、左侧胸肌和腿肌样本进行分析。试验结果表明,与对照组相比母源性添加DHEA对子代肉鸡日采食量、日增体质量均无显著差异(P0.05),但母源性添加DHEA却可极显著地降低其料肉比(P0.01)。对子代公鸡而言,与对照组相比母源性添加高剂量的DHEA可显著地升高血清BG(P0.01)、NEFA(P0.05)和HDL-C(P0.05)的含量,极显著地降低肝脏组织中TG的含量(P0.01),但对血清TC、TG含量均无显著影响(P0.05);不同剂量的DHEA对其血清中T3、T4、GLU和Leptin的含量均无显著的影响(P0.05),但低剂量的DHEA却可显著地升高T3/T4值(P0.05)。对子代母鸡而言,与对照组相比母源性添加低剂量的DHEA可极显著地升高血清BG的含量(P0.01);高剂量的DHEA可极显著地升高血清TC、TG、NEFA和GLU的含量(P0.01),低剂量的DHEA可显著地升高HDL-C的含量(P0.05)和T4含量(P0.01),但却降低T3/T4值(P0.05)。母源性添加DHEA可显著地升高子代公鸡的胸肌率和腿肌率(P0.05),但对子代母鸡的胸肌率和腿肌率无显著影响(P0.05);同时母源性添加不同剂量的DHEA均可显著地降低腿肌肌纤维直径(P0.01),极显著地升高腿肌肌纤维密度(P0.01);高剂量的DHEA可极显著地降低胸肌肌纤维直径(P0.01),低剂量的DHEA可显著地降低胸肌肌纤维直径(P0.05),但不同剂量的DHEA均可极显著地升高胸肌肌纤维密度(P0.01)。结论提示,母源性添加DHEA可降低子代肉鸡脂肪的沉积和改善其肌肉品质。     

脱氢表雄酮(DHEA)对鸡胚原代肝细胞cAMP/PKA信号通路和cAMP反应元件结合蛋白(CREB)的影响与调节

控制肉鸡脂肪过多沉积是肉鸡生产中亟待解决的问题。脱氢表雄酮(dehydroepiandrosterone,DHEA)是人体分泌最为丰富的肾上腺类固醇激素,可经由类固醇激素受体介导发挥生理功能,降低机体生脂能力。本研究以鸡胚原代肝细胞为研究对象,选用含DHEA终浓度为0(对照)、0.01、0.1、1.0、10和100μmol/L的培养液孵育肝细胞20min后收集细胞,放射免疫测定法(RIA)检测胞内cAMP水平。结果发现,0.1～100μmol/L DHEA孵育肝细胞均可显著提高胞内cAMP水平(P<0.05),其中0.1μmol/L DHEA效果最为显著(P<0.01)。0.1μmol/L DHEA孵育肝细胞20min或1h后收集细胞,RIA法分别检测胞内腺苷酸环化酶(adenylate cyclase,AC)和磷酸二酯酶(phosphodiesterase,PDE)活性,(γ-32P)ATP掺入法测定cAMP依赖性蛋白激酶A(protein kinase A,PKA)活性,Western blot法测定cAMP反应元件结合蛋白(cAMP-response element binding protein,CREB)磷酸化水平。结果显示,0.1μmol/L DHEA孵育肝细胞20min可显著降低胞内PDE活性(P<0.05),提高PKA活性(P<0.05),但对AC活性无显著性影响(P>0.05)。0.1μmol/L DHEA处理肝细胞1h可显著提高CREB蛋白磷酸化水平(P<0.05),且这种效应可被PKA抑制剂阻断(P>0.05)。本研究结果提示,DHEA调控肉鸡肝脏脂肪代谢,降低脂肪沉积的机制可能与激活胞内cAMP/PKA信号系统,活化转录因子CREB有关。     

Depressed DHEA and increased sickness response behaviors in lame dairy cows with inflammatory foot lesions

Lameness is a multifactorial condition influenced by the environment, genetics, management and nutrition. Detection of lameness is subjective and currently limited to visual locomotion observations which lack reliability and sensitivity. The objective of this study was to search for potential biomarkers of inflammatory foot lesions that underlie most cases of lameness in dairy cows, with a focus on the sickness response and relevant endocrine, immune and behavioral changes. Serum and peripheral blood mononuclear cells (PBMC) were collected from eight sound and eight lame high-producing Holstein cows. Immune cell activation was investigated in PBMCs using a candidate gene approach in which the expression of pro-opiomelanocortin, interleukin-1beta, l-selectin, matrix metalloproteinase-9 and glucocorticoid receptor-alpha was measured via quantitative real time-RT-PCR. Endocrine changes were investigated by monitoring serum concentrations of cortisol and dehydroepiandrosterone (DHEA). Additionally, systematic behavioral observations were carried out to characterize a behavioral profile associated with a sickness response typical of this condition. Lame cows showed significantly lower eating (P=0.01) and ruminating (P=0.01) behaviors and higher incidence of self-grooming (P=0.04) compared to sound cows. Lame cows also showed a 23% decrease in serum DHEA (P=0.01) and 65% higher cortisol:DHEA ratio (P=0.06) compared to sound cows. However, no significant differences were found in candidate gene expression between lame and sound cows. In association with sickness behaviors, serum DHEA concentration and cortisol:DHEA ratio are promising objective indicators of inflammatory foot lesions in dairy cattle and may be useful as diagnostic targets for animals in need of treatment.