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1.
精胺抑制人精子的体外受精能力   总被引:7,自引:1,他引:6  
石其贤  钟翠玲 《生理学报》1991,43(5):480-488
以精子穿透去透明带仓鼠卵试验(SPA)为模型,评价了精胺对人精子体外受精能力的影响。精胺(0.25—8.0mmol/L)可抑制人精子体外获能和受精,其抑制作用与精胺浓度呈正相关,此种抑制作用是可逆的。用 HPLC 测定精子精胺含量表明,精子获能后精胺含量明显下降。dbcAMP(0.5—1.0mmol/L)或咖啡因(10mmol/L)可拮抗精胺抑制人精子体外获能。其拮抗作用随 dbcAMP 浓度而增强。钙离子载体 A 23187 2/μmol/L 或胰蛋白酶0.05%均可拮抗精胺抑制人精子穿卵率。上述结果提示,精胺可能通过降低精子 cAMP 含量和抑制钙内流或顶体酶活性,从而阻止人精子体外获能和受精。  相似文献   

2.
γ-氨基丁酸诱发人精子顶体反应及其受精能力   总被引:11,自引:1,他引:10  
Yuan YY  He CN  Shi QX 《生理学报》1998,50(3):326-332
本文的目的是为了探讨γ-氨基丁酸是否可激发人精子顶体反应,受主其可能的作用方式。实验采用金霉素荧光染色法,胞内游离C62+测定和精子穿透去透明带仓鼠卵试验,分别评价GABA诱发人精子AR及其穿卵能力。结果表明;GABA可诱发人获能精子发生AR,且随精子获得进程而显著增加,并存在明显的量效关系,该作用可被P4加强。  相似文献   

3.
该文研究了丙烯酰胺在体外对人成熟精子功能的影响。不同浓度(0,2,10,50,250,1 000μmol/L)的丙烯酰胺溶液在体外处理人成熟精子,利用伊红苯胺黑染色、计算机辅助精子分析系统、金霉素染色、精子单细胞钙成像等方法检测精子活力、运动、获能、顶体反应和胞内钙动员等生理功能。结果显示,不同浓度的丙烯酰胺溶液对人成熟精子活率、运动、获能、顶体反应以及胞内钙动员等生理功能均未有显著影响。推测丙烯酰胺体外急性染毒在短时间内并不抑制人成熟精子功能。  相似文献   

4.
该文研究邻苯二甲酸二(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]在体外对人成熟精子功能的影响。用0,0.1,1,10,100μmol/L DEHP处理离体人成熟精子后,利用伊红苯胺黑染色、计算机辅助精子分析系统、精子穿甲基纤维素实验、金霉素染色等方法检测精子存活率、运动、超活化、获能、顶体反应等生理功能。结果显示,DEHP在短时间内不影响精子存活率,但是抑制精子运动、超活化以及孕酮诱导的获能和顶体反应。推测DEHP体外急性染毒会抑制人成熟精子功能。  相似文献   

5.
钙调素(CaM)拮抗剂三氟拉嗪(TFP)在10~100 μmol/L浓度范围内对豚鼠精子获能和顶体反应具有极显著的促进作用,且不依赖于外源Ca2+的存在.Forskolin,dbcAMP和咖啡因对非同步培养系统获能早期豚鼠精子的顶体反应有显著的促进作用,但对同步培养系统获能早期精子的顶体反应无显著影响.若在同步培养系统获能培养较长时间(15h)使精子获能,则这3种药物对顶体反应均具有显著的促进作用,且不依赖外源Ca2+的存在.蛋白激酶C(PKC)激活剂PMA和PDB对获能前期豚鼠精子的顶体反应无显著影响,但对获能精子的顶体反应有显著的促进作用,且这种促进作用也不依赖于外源Ca2+的存在.相反,PKC抑制剂stau-rosporine对顶体反应有显著的抑制作用.  相似文献   

6.
重组人卵透明带蛋白(rhZP3)的生物活性研究   总被引:2,自引:0,他引:2       下载免费PDF全文
为了研究毕赤酵母表达的重组人卵透明带蛋白(rhZP3)的生物活性,分别用空白培养液,含孕酮或rhZP3的培养液对人精子进行顶体诱发实验,用考马斯亮蓝染色法对顶体状态进行评价;用不同浓度的rhZP3以及空白培养液分别处理精子,然后再与卵子进行结合实验,观察经过不同处理的精子在精卵结合中的情况;用抗rhZP3抗血清与阴性血清分别处理卵子,再与精子进行结合实验,观察经过不同处理后的卵子在精卵结合中的情况。rhZP3诱发顶体反应实验结果显示,rhZP3处理组与空白对照组之间差异显著(P<0.01);精卵结合实验结果显示,各实验组和对照组之间存在显著性差异(P<0.01),rhZP3、抗rhZP3抗体均能抑制精卵结合。实验结果表明,rhZP3具有天然人卵透明带蛋白相似的活性。  相似文献   

7.
猪卵母细胞的体外受精及多精受精   总被引:4,自引:0,他引:4  
对用于猪体外受精(IVF)的研究方法和技术,如传统的液滴IVF、透明带下注射精子受精(SUZI)、卵母细胞质内单精注射受精(ICSI)及细管IVF等进行了简述。与其它动物相比,进行猪卵的体外受精研究,多精受精现象特别明显。大量的研究表明,猪卵的多精受精不但与其品种特性有关,而且与卵母细胞成熟的程度、透明带的异常、受精时获能精子的浓度、输卵管分泌物、受精液蛋白添加成分、NaHCO3浓度、咖啡因、pH值以及温度等因素密切相关。  相似文献   

8.
大熊猫体外受精的初报   总被引:1,自引:0,他引:1  
我们在大熊猫精子体外获能与异种穿卵成功的基础上,又进行了大熊猫体外受精的首次尝试。 大熊猫卵母细胞取自刚死的育龄雌性大熊猫的卵巢,经体外培养16小时后,加入在体外已获能的大熊猫精子,进行体外受精。发现精子头能穿入卵透明带并进卵膜,继续培养19小时后因污染不幸夭亡。这是大熊猫同种体外受精的第一次报道。这一新进展表明,对研究试管大熊猫又跨近了一步。人们将有可能利用这种生物高技术去主动地拯救大熊猫,为珍稀动物物种的繁殖和保存开劈了一条新途  相似文献   

9.
羊精子体外获能   总被引:4,自引:0,他引:4  
本文发展了一种羊精子体外获能培养基——mTs或RSCM。羊精子在该培养基中(39℃.pH7.8和5% CO_2,95%空气)预先培养7小时,可使大部分精子获能。获能精子呈现超激活运动,并可穿透去透明带仓鼠卵,穿透率分别为78.5±14.3%和96.7±2.3%,这种作用可被同种精浆逆转。获能精子与同种卵的受精率为83.3%。16个受精卵等量移入2只假孕兔输卵管壶腹部中。72小时后回收到12个胚胎。其中6个胚胎已发育为4—8细胞阶段,将这些细胞等量移入2只受体母羊输卵管壶腹部。其中1只妊娠,并维持到2个月之久。  相似文献   

10.
本文从中药赤小豆(Phaseolus Calcaratus,Roxb)中分离出一种胰蛋白酶抑制剂。通过一系列酶促反应动力学的研究表明,赤小豆抑制剂对胰蛋白酶有较强的不可逆竞争性抑制作用。其Km和ki值分别为1.43×10~(-3)mmol/L和2.4×10~(-6)mmol/L。  相似文献   

11.
Allosteric mechanisms are pervasive in nature, but human-designed allosteric perturbagens are rare. The history of KRASG12C inhibitor development suggests that covalent chemistry may be a key to expanding the armamentarium of allosteric inhibitors. In that effort, irreversible targeting of a cysteine converted a non-deal allosteric binding pocket and low affinity ligands into a tractable drugging strategy. Here we examine the feasibility of expanding this approach to other allosteric pockets of RAS and kinase family members, given that both protein families are regulators of vital cellular processes that are often dysregulated in cancer and other human diseases. Moreover, these heavily studied families are the subject of numerous drug development campaigns that have resulted, sometimes serendipitously, in the discovery of allosteric inhibitors. We consequently conducted a comprehensive search for cysteines, a commonly targeted amino acid for covalent drugs, using AlphaFold-generated structures of those families. This new analysis presents potential opportunities for allosteric targeting of validated and understudied drug targets, with an emphasis on cancer therapy.  相似文献   

12.
A novel class of potent and selective inhibitors of KDR incorporating an indazole moiety 1 is reported. The discovery, synthesis, and structure–activity relationships of this series of inhibitors have been investigated. The most promising compounds were also profiled to determine their pharmacokinetic properties and evaluated in a VEGF-induced vascular permeability assay.  相似文献   

13.
Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhibitor 4, discovered through high-throughput screening, were synthesized to investigate structure-activity relationships in this inhibitor series. Systematic modifications of 4 led to the discovery of MMP-13 inhibitors 20 and 24 which are more selective than 4 against other MMPs. Compound 20 is also approximately fivefold more potent as an MMP-13 inhibitor than the original HTS-derived lead compound 4.  相似文献   

14.
A series of substituted 2-(aminoheteroaryl)-thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy.  相似文献   

15.
Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally.  相似文献   

16.
Proteinase inhibitors are released to a smaller extent from soybeans which have been pre-equilibrated to an atmosphere of high relative humidity (r.h.) compared to those equilibrated to low r.h. Seeds pre-equilibrated to high r.h. also exhibited better germination. Regardless of the states of seed hydration, both Kunitz and Bowman-Birk soybean trypsin inhibitors are released in parallel with respect to each other and to other proteins at germination times up to 100 hr. After 48 hr of germination, new forms of trypsin inhibitor appear in the leachate which react with anti-Bowman-Birk trypsin inhibitor antibodies. No new forms of Kunitz trypsin inhibitor were observed immunochemically during the first 100 hr of germination.  相似文献   

17.
Crystal structure of the complex between porcine beta-trypsin and the second domain of the Kazal-type ovomucoid turkey egg white trypsin inhibitor (OMTKY2) has been determined at 1.9A resolution. A peptide fragment from the first domain has been crystallized with the complex. Restrained-refinement of the structure led to an R-factor of 0.19 for the 32206 reflections. OMTKY2 exhibits the canonical Kazal-type fold with a central alpha-helix and a short two-stranded anti-parallel beta-sheet. The carbonyl carbon of the reactive site prefers trigonal geometry. The reactive site loop geometry of the inhibitor is complementary to the surface and charge of the binding site in beta-trypsin.  相似文献   

18.
Hit compound 1, a selective noradrenaline re-uptake transporter (NET) inhibitor was optimised to build in potency at the serotonin re-uptake transporter (SERT) whilst maintaining selectivity against the dopamine re-uptake transporter (DAT). During the optimisation of 1 it became clear that selectivity against the Kv11.1 potassium ion channel (hERG) was also a parameter for optimisation within the series. Discrete structural changes to the molecule as well as a lowering of global cLogP successfully increased the hERG selectivity to afford compound 11m, which was efficacious in a mouse model of inflammatory pain, complete Freund’s adjuvant (CFA) induced thermal hyperalgesia and a rat model of neuropathic pain, spinal nerve ligation (SNL) induced mechanical allodynia.  相似文献   

19.
M Crabos  I W Wainer  J F Cloix 《FEBS letters》1984,176(1):223-228
This study was undertaken to assess endogenous Na+,K+-ATPase inhibitors in both plasma and urine in the same subjects. Samples were chromatographed on reverse-phase HPLC using an acetonitrile gradient and the eluent screened using Na+,K+-ATPase inhibition and cross-reaction with anti-digoxin antibodies. The donors were divided into inhibiting and non-inhibiting subjects using a previously described method, plasma action on ouabain binding and on Na+,K+-ATPase activity. Three Na+,K+-ATPase inhibitors (1P, 2P and 3P) were detectable in plasma; the antibodies cross-reaction of the peaks 2P and 3P were larger than that of peak 1P. The peaks 2P and 3P were significantly higher in inhibiting subjects as compared to non-inhibiting subjects. The 24-h urine is resolved into two peaks inhibiting Na+,K+-ATPase activity (1U and 2U). Peak 2U cross-reacted with anti-digoxin antibodies to a greater extent than peak 1U and is significantly larger in inhibiting subjects in terms of Na+,K+-ATPase inhibition. These data support the heterogeneity of human Na+,K+-ATPase inhibitor in both plasma and urine.  相似文献   

20.
A set of bisphosphonate matrix metalloproteinase (MMP) inhibitors was investigated for inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, some of which are overexpressed in hypoxic tumors. Some of the bisphosphonate revealed to be very potent inhibitors (in the low nanomolar range) of the cytosolic isoform CA II and the membrane-bound CA IX, XII and XIV isozymes, a feature useful for considering them as interesting compounds for bone resorption inhibition applications. We suggest here that it is possible to develop dual enzyme inhibitors bearing bisphosphonate moieties that may target both MMPs and CAs, two families of enzymes involved in tumor formation, growth, and metastasis.  相似文献   

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