CN110339205A - 富氢水组合物在抑制六价铬诱导的df-1细胞内质网应激及自噬中的应用 - Google Patents
富氢水组合物在抑制六价铬诱导的df-1细胞内质网应激及自噬中的应用 Download PDFInfo
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Abstract
本发明公开富氢水组合物在抑制六价铬诱导的DF‑1细胞内质网应激及自噬中的应用，所述富氢水组合物中含有：H2 0.6mM‑1.1mM、海藻酸钠1.8‑2.4g/L、甘露聚糖1.2‑1.6g/L；本发明的富氢水组合物可以保持富氢水中氢气含量的稳定；而且，本发明的富氢水组合物对Cr(VI)诱导的DF‑1细胞COX‑2表达量增加能够起到抑制作用，从而能抑制由COX‑2上升引起的DF‑1细胞内质网应激和过度自噬。
Description
技术领域
本发明涉及富氢水组合物的医药用途技术领域，具体涉及富氢水组合物在抑制六价铬诱导的DF-1细胞内质网应激及自噬中的应用。
背景技术
内质网(ER)是活细胞中精确的膜系统，广泛存在于真核生物的细胞中，参与蛋白质折叠并维持钙稳态。高效的ER功能对于正常的细胞活动是必不可少的。当ER功能受到一些诸如缺血缺氧、营养不足、同型半胱氨酸等内部或外部刺激的干扰时，内质网不能履行正常的生理功能。当发生内质网应激时，未折叠蛋白或错误折叠蛋白会随之积累，而当这些蛋白积累到一定程度以后，则会给内质网一个反馈信号，引发负向调控，促使内质网对积累的蛋白质进行处理，这种处理包括停止翻译、加速降解和折叠变强等一系列现象，最终减少蛋白质在内质网上的蓄积，这种减少蓄积的过程就叫做内质网应激。早期内质网应激是细胞自我保护的生理性应激，但是当错误的未折叠蛋白超过内质网的处理能力，细胞将产生一系列应答，称为未折叠蛋白反应，经过一系列的信号传递，最后启动细胞凋亡、自噬等。
自噬是真核生物中一种高度保守的大规模蛋白质降解途径，它从细胞质部分开始，将未折叠的蛋白和受损的细胞器包裹在自噬体中，然后成熟的自噬体与溶酶体融合形成自噬溶酶体，螯合物被各种溶酶体水解酶降解，最后氨基酸被循环用于大分子合成和能源生产。在生理条件下，自噬保持在相对低的水平，以通过能量和细胞构建材料的更新来维持细胞稳态。然而，过度自噬将自噬从一种保护机制转变为一种损害机制，过度降解细胞基本蛋白和细胞器导致细胞功能受损，甚至发生自噬性细胞死亡。氧化应激、代谢应激和饥饿、重金属等多种因素可诱导过度自噬。
环氧合酶(COX)包括COX-1(由前列腺素H合成酶1基因编码，PTGS1)和COX-2(由前列腺素H合酶2基因编码，PTGS2)。它们能够催化前列腺素合成的限速步骤。一般而言，COX-2在正常情况下保持在低水平，但在炎症刺激、细胞因子、激素和不同生长因子的作用下可迅速增加。COX-2是关键的限速酶，而COX-2介导的PGE2合成控制涉及许多功能障碍和炎症。研究表明，六价铬可以诱导DF-1细胞中COX-2的上升，内质网应激和细胞自噬的形成；COX-2在六价铬诱导的DF-1细胞内质网应激和自噬间起到关键作用。但对于如何抑制六价铬引起的DF-1细胞中COX-2上升，以及由COX-2上升引起的DF-1细胞内质网应激和过度自噬，目前尚缺少相关研究。
富氢水是指含有氢气的水，具有很强的还原功能，可促进干扰素表达并使肿瘤的体积和质量下降；抑制大鼠急性一氧化碳(carbon monoxide，CO)中毒后大脑皮层的凋亡；降低促炎因子的表达缓解因氧化应激引起的组织炎症；饱和氢盐水可减轻大鼠原位肝移植术后急性肾损伤。但目前还未见有关于富氢水在抑制六价铬引起的DF-1细胞中COX-2上升，以及由COX-2上升引起的DF-1细胞内质网应激和过度自噬的报道。
而且，由于氢气分子量小等原因，氢气渗透性极强，因此，氢气非常容易通过包装材料和微小的缝隙进行扩散，而使富氢产品中的氢气含量减少，甚至不含氢气，给富氢产品的储存和运输带来很大的困难，限制了富氢产品的推广应用。
发明内容
针对上述现有技术，本发明提供了一种富氢水组合物，可以保持富氢水中氢气含量的稳定；而且，本发明的富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达量增加能够起到抑制作用，从而能抑制由COX-2上升引起的DF-1细胞内质网应激和过度自噬。
本发明的第一方面，提供一种富氢水组合物，所述富氢水组合物中含有：H20.6mM-1.1mM、海藻酸钠1.8-2.4g/L、甘露聚糖1.2-1.6g/L。
本发明的第二方面，提供上述富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞中COX-2过表达的药物中的应用。
本发明的第三方面，提供上述富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞内质网应激的药物中的应用。
上述应用中，所述内质网应激是由Cr(VI)诱导的DF-1细胞中COX-2过表达引起的。
本发明的第四方面，提供上述富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞过度自噬的药物中的应用。
上述应用中，所述富氢水组合物通过如下1)或2)中至少一项的途径来抑制Cr(VI)诱导的DF-1细胞过度自噬；
1)抑制COX-2过表达；
2)下调LC3及Beclin1蛋白的表达、P62蛋白的降解。
本发明的第五方面，提供一种富氢培养基(HRM)，所述富氢培养基由如下方法制备而成：
将DMEM干粉培养基用上述富氢水组合物溶解，并按3.5-4.0g/L添加NaHCO3，即配制得到富氢培养基。
本发明的第六方面，提供上述富氢培养基在构建研究富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达、内质网应激和细胞过度自噬影响的体系中的用途。
本发明的有益效果：
(1)本发明首次将富氢水和海藻酸钠、甘露聚糖复配，制成富氢水组合物；其中，海藻酸钠和甘露聚糖在水溶液中能够形成交联分枝状的骨架结构，可以对富氢水中的氢气分子起到吸附、包裹作用，从而有效保持富氢水中氢气含量的稳定。
(2)本发明所制备的富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达量增加能够起到抑制作用，从而能抑制由COX-2上升引起的DF-1细胞内质网应激和过度自噬。
附图说明：
图1：富氢培养基(HRM)中H2浓度检测。
图2：DF-1细胞活性检测；将细胞在不含(Con)或含20μM Cr(VI)的DMEM培养基中培养20小时；在富氢培养基中培养20小时；在含20μM Cr(VI)的富氢培养基中培养20小时。3-MA(100μM)和Rapa(1μM)分别作为自噬阴性和阳性对照，4-PBA(1mM)及Tg(10μM)分别作为内质网应激阴性和阳性对照；数据表示为平均值±标准差(n＝3)。没有共同字母的表示具有显著差异(P<0.05)。
图3：HRM对Cr(VI)诱导的GRP78/Bip和PERK蛋白表达的影响；(A)通过WesternBlot检测GRP78/Bip及其蛋白水平定量分析。(B)PERK蛋白水平的定量分析。数据表示为平均值±标准差(n＝3)。没有共同字母的表示具有显著差异(P<0.05)。
图4：HRM对Cr(VI)诱导的自噬相关蛋白水平的影响。(A)通过Western Blot检测LC3-I和LC3-II及其蛋白水平定量分析。(B)通过Western Blot检测P62及其蛋白水平定量分析。(C)通过Western Blot检测Beclin1及其蛋白水平定量分析。数据表示为平均值±标准差(n＝3)。没有共同字母的表示具有显着差异(P<0.05)。
图5：HRM对Cr(VI)诱导的COX-2表达的影响。(A)HRM对COX-2蛋白水平变化的定量分析。(B)自噬及内质网应激对COX-2蛋白水平变化的定量分析。(C)通过Western Blot检测LC3-I和LC3-II及其蛋白水平定量分析。(D)通过Western Blot检测P62及其蛋白水平定量分析。(E)通过Western Blot检测GRP78/Bip及其蛋白水平定量分析。NS-398(20μM)是COX-2抑制剂。数据表示为平均值±标准差(n＝3)。没有共同字母的表示具有显著差异(P<0.05)。
具体实施方式
应该指出，以下详细说明都是例示性的，旨在对本申请提供进一步的说明。除非另有指明，本文使用的所有技术和科学术语具有与本申请所属技术领域的普通技术人员通常理解的相同含义。
正如背景技术部分介绍的，自噬是许多生理和病理过程所必需的，并且在维持细胞代谢平衡和体内平衡中起关键作用。自噬在大多数的情况下对机体有保护作用，但当自噬被过度激活时，会对机体产生损害，甚至引起自噬性死亡。
自噬的发生受多种不同分子机制的调控，目前已发现30多个与自噬相关的基因。因此，对于不同种类细胞过度自噬的调控，其采用的方法也各有不同。
六价铬可以诱导DF-1细胞中COX-2的上升，内质网应激和细胞自噬的形成。但目前对于DF-1细胞由上述机制引起的细胞自噬尚缺少有效的调控手段。
富氢水作为一种非常有效的抗氧化剂，其能激活细胞，促进人体的新陈代谢，对多种慢性疾病具有辅助治疗的作用。但由于氢气非常容易通过包装材料和微小的缝隙进行扩散，而使富氢产品中的氢气含量减少，甚至不含氢气，从而严重制约了富氢产品的推广应用。
基于此，本发明首先提供了一种富氢水组合物，在本发明的富氢水组合物中，其氢气浓度为0.6mM-1.1mM，该浓度下的氢气能够产生有效的生物学效应；为减少氢气的扩散，本发明发现，通过添加一定量的海藻酸钠和甘露聚糖，能够在水溶液中能够形成交联分枝状的骨架结构，可以对富氢水中的氢气分子起到吸附、包裹作用，从而有效保持富氢水中氢气含量的稳定；同时，本发明还意外的发现，海藻酸钠和甘露聚糖能够与氢气产生协同增效作用，与单独使用氢气相比，其生物学效应有了显著的提高。
为考察本发明的富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达、内质网应激和细胞过度自噬的影响，本发明还构建了一种富氢培养基(HRM)，所述富氢培养基是将DMEM干粉培养基用上述富氢水组合物溶解，并按3.5-4.0g/L添加NaHCO3，即配制得到富氢培养基。
利用所配制的富氢培养基研究发现，本发明所制备的富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达量增加能够起到抑制作用，从而能抑制由COX-2上升引起的DF-1细胞内质网应激和过度自噬，由此提出了本发明。
为了使得本领域技术人员能够更加清楚地了解本申请的技术方案，以下将结合具体的实施例详细说明本申请的技术方案。
本发明实施例中所用的试验材料均为本领域常规的试验材料，均可通过商业渠道购买得到。其中，部分试验材料具体如下：
实施例1：富氢水组合物及富氢培养基的制备
1.富氢水组合物：
在氢气浓度为0.6mM-1.1mM的富氢水中加入海藻酸钠和甘露聚糖，使海藻酸钠浓度为2.2g/L、甘露聚糖浓度为1.4g/L，即制备得到富氢水组合物。
2.富氢培养基(HRM)：
将DMEM干粉培养基用上述富氢水组合物溶解，每1gDMEM干粉培养基用50mL富氢水组合物溶解，并添加NaHCO3，每1L富氢培养基中添加3.7g NaHCO3，即配制得到富氢培养基。
试验例1：
将实施例1制备的富氢培养基置于培养皿中，每隔1h采用溶解氢含量测试仪ENH-1000(Trustlex Co.,Osaka,Japan)检测HRM中氢含量。
作为对比，用相同氢气浓度的富氢水溶解DMEM干粉培养基，并添加NaHCO3，制备得到对照富氢培养基。
将对照富氢培养基采用相同的方法检测氢含量，结果见图1。由图1可以看出，采用本发明的富氢水组合物制备的富氢培养基，培养基中的分子H2水平能够持续至少8-9小时；而对照富氢培养基的H2水平维持不到1小时。
实施例2：富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达、内质网应激和细胞过度自噬的影响研究
1.试验方法：
1.1细胞培养
试验所用DF-1细胞严格按照提供者的说明进行培养。DF-1细胞使用的培养基为加入10％体积的胎牛血清和1％体积的青链霉素混合液的DMEM，于37℃，5％二氧化碳培养箱培养。
1.2细胞处理
培养DF-1细胞进行试验生长，并与Cr(VI)和/或HRM在5％二氧化碳中于37℃温育20小时。本试验中的四个处理组如下：(1)对照组：在DMEM培养基中培养20小时；(2)Cr(VI)处理组：在含Cr(20μM)的DMEM中培养20小时；(3)HRM处理组：在富氢培养基(HRM)中培养20小时；(4)HRM+Cr(VI)处理组：在含Cr(20μM)的富氢培养基(HRM)中培养20小时；HRM中均添加5％体积的胎牛血清，20小时后收获细胞用于分析。
其中，HRM为实施例1制备得到。
1.3细胞活力测定
细胞处理后，采用CCK-8检测试剂盒对其进行细胞活力测定。
1.4 Western Blot检测
细胞处理后，用PBS(4℃)洗涤细胞，并在冰上与补充有1mM苯基甲磺酰氟(PMSF)的RIPA裂解缓冲液共孵育10分钟。然后通过在4℃以12,000g离心15分钟澄清细胞裂解物。使用BCA蛋白质测定试剂盒(Beyotime Biotechnology，Jiangsu，China)测定蛋白浓度。将等量的蛋白样品在5×SDSPAGE上样缓冲液中稀释并煮沸5分钟。通过SDS-PAGE分离蛋白质(20μg)并转移到0.22μm聚偏二氟乙烯(PVDF)膜(Merck millipore，Massachusetts，USA)上。在含有5％脱脂奶粉的TBST室温封闭1小时后，将膜在4℃下与针对Beclin1的稀释一抗(1：1000，Proteintech，USA)，LC3Ⅱ(1：1000，Abcam，英国)，P62(1：1000，Proteintech，USA)和GRP78/Bip(1：1000，Beyotime，中国)。然后，用含有0.1％吐温20的TBST将膜洗涤三次，每次10分钟。将膜与合适的二抗在室温下孵育1小时。最后，通过使用ECL Western DetectionReagents测量每种靶蛋白。然后通过Image J软件分析蛋白质水平。将每个条带的密度归一化至其各自的加载对照(GAPDH)。
1.5 ELISA检测
使用细胞膜和细胞核蛋白质提取试剂盒(Beyotime Biotechnology，江苏，中国)提取DF-1细胞蛋白用于检测。用酶联免疫吸附试验(ELISA)试剂盒测定血清PERK和COX-2蛋白水平：PERK(Mlbiotech，中国上海)和COX-2(Mlbiotech，中国上海)根据制造商的说明进行试验。用自动化酶标仪在450nm读取吸光度，并通过标准曲线标准化所有吸光度结果。
1.6统计分析
本试验所有数据使用SPSS 24.0生物统计软件进行One-Way ANOVA统计分析，数值采用平均值±标准差(mean±SD)的形式表示，同时采用Graph Pad Prism 7.0软件作图，P<0.05表示差异显著。所有试验数据均重复测定3次。
2.实验结果
2.1 DF-1细胞活性检测
雷帕霉素(Rapa)、3-MA分别作为自噬的诱导剂与抑制剂，Tg、4-PBA作为内质网应激的诱导剂与抑制剂，分别处理细胞，以验证自噬与内质网应激对细胞活性的影响。采用CCK-8法检测细胞活性，结果(图2)显示，Cr(VI)处理组细胞活性较对照组显著下降，而3-MA+Cr(VI)处理组中，3-MA抑制自噬后细胞活性较Cr(VI)处理组有所上升，说明Cr(VI)引起细胞发生过度自噬，对细胞产生损伤；HRM与3-MA有相同的作用效果，与Cr(VI)处理组相比细胞活性显著上升，由此推测HRM可能通过抑制Cr(VI)引起的过度自噬对细胞产生保护作用；同时结果显示4-PBA+Cr处理组细胞存活率较Cr(VI)处理组显著升高，由此推测铬可通过激活内质网应激诱导自噬，因此接下来检测细胞内质网应激及自噬的相关指标，从而验证此推测。
2.2 HRM通过抑制PERK和GRP78/Bip的蛋白水平抑制Cr(VI)诱导的内质网应激
GRP78/Bip和PERK是内质网应激的两个重要指标，因此检测其蛋白水平变化。我们的研究结果(图3)表明Cr(VI)诱导DF-1细胞发生内质网应激，Cr(VI)处理组内质网应激的标志性蛋白GRP78/Bip和PERK的蛋白水平显著高于对照组。同时HRM+Cr(VI)处理组中GRP78/Bip和PERK蛋白水平显著低于Cr(VI)组。这些结果表明HRM可以减轻由Cr(VI)引起的内质网应激。
2.3 HRM通过改变LC3、P62、Beclin1蛋白的水平抑制Cr(VI)诱导的自噬
LC3是酵母Atg8的自噬体直系同源物。已经显示脂质形式的LC3(LC3-II)是哺乳动物中的自噬体标记物。P62参与泛素-蛋白酶体系统和自噬-溶酶体系统的降解过程，并且是自噬的标记蛋白。Beclin1是自噬体形成的必需分子，作为一种分子平台，它可以介导自噬相关蛋白定位于吞噬泡，并与各种蛋白反应，调节自噬体的形成和成熟。当DF-1细胞暴露于Cr(VI)时，LC3-II(图4-A)及Beclin1(图4-C)的表达水平高于对照组，P62(图4-B)的蛋白水平低于对照组。然而，通过HRM处理可以显著改变这种变化，表明HRM可以抑制Cr(VI)诱导的自噬。
2.4 HRM对Cr(VI)诱导的DF-1细胞COX-2表达量增加的抑制作用
为了探究COX-2在Cr(VI)诱导的细胞自噬及内质网应激中的作用及HRM处理是否对COX-2产生影响，因此检测了COX-2的表达水平。当细胞暴露于Cr(VI)时，COX-2水平较对照组显著增加。相反，在HRM+Cr(VI)处理组中，COX-2水平较Cr(VI)处理组显著下降(图5-A)，表明HRM可以抑制Cr(VI)诱导的COX-2水平增加。为验证COX-2与细胞自噬及内质网应激的关系，因此添加NS-398，并检测自噬及内质网应激相关指标变化。添加NS-398后，与Cr(VI)处理组相比，LC3-II及GRP78/Bip蛋白水平显著下降且P62的降解水平显著增强(图5C-E)；同时添加Rapa及Tg后，COX-2水平较对照组显著升高，而添加3-MA及4-PBA后，COX-2水平较Cr(VI)组有所下降(图5-B)，说明COX-2在Cr(VI)诱导的自噬及内质网应激中发挥着重要作用。
综上，Cr(VI)可显著诱导自噬相关蛋白(Beclin1和LC3II/I)，ER应激相关蛋白(GRP78/Bip和PERK)及COX-2表达，抑制自噬相关蛋白P62的降解，而富氢培养基可以缓解Cr(VI)诱导的上述蛋白表达量的变化。证实富氢培养基可以通过内质网应激途径改善Cr(VI)诱导的自噬，这为富氢培养基介导的保护作用的分子机制提供了基础。因此，富氢水是可以在某些条件下抑制应激诱导的自噬的有用天然药剂。
以上所述仅为本申请的优选实施例而已，并不用于限制本申请，对于本领域的技术人员来说，本申请可以有各种更改和变化。凡在本申请的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本申请的保护范围之内。
Claims (8)
1.一种富氢水组合物，其特征在于，所述富氢水组合物中含有：H2 0.6mM-1.1mM、海藻酸钠1.8-2.4g/L、甘露聚糖1.2-1.6g/L。
2.权利要求1所述的富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞中COX-2过表达的药物中的应用。
3.权利要求1所述的富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞内质网应激的药物中的应用。
4.根据权利要求3所述的应用，其特征在于，所述内质网应激是由Cr(VI)诱导的DF-1细胞中COX-2过表达引起的。
5.权利要求1所述的富氢水组合物在制备抑制Cr(VI)诱导的DF-1细胞过度自噬的药物中的应用。
6.根据权利要求5所述的应用，其特征在于，所述富氢水组合物通过如下1)或2)中至少一项的途径来抑制Cr(VI)诱导的DF-1细胞过度自噬；
1)抑制COX-2过表达；
2)下调LC3及Beclin1蛋白的表达、P62蛋白的降解。
7.一种富氢培养基，其特征在于，所述富氢培养基由如下方法制备而成：
将DMEM干粉培养基用权利要求1所述的富氢水组合物溶解，并按3.5-4.0g/L添加NaHCO3，即配制得到富氢培养基。
8.权利要求7所述的富氢培养基在构建研究富氢水组合物对Cr(VI)诱导的DF-1细胞COX-2表达、内质网应激和细胞过度自噬影响的体系中的用途。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114984046A (zh) * | 2022-05-05 | 2022-09-02 | 山东鑫谷健康产业有限公司 | 富氢水组合物及其在缓解动物温度应激中的应用 |
Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1556795A (zh) * | 2001-09-21 | 2004-12-22 | 霍夫曼-拉罗奇有限公司 | 3－脱氧－维生素d3类似物酯 |
| CN101138647A (zh) * | 2006-09-08 | 2008-03-12 | 远东纺织股份有限公司 | 制备覆膜基材用的组成物及覆膜基材的制法及其制品 |
| CN101528691A (zh) * | 2006-08-22 | 2009-09-09 | 兰贝克赛实验室有限公司 | 基质金属蛋白酶抑制剂 |
| CN102000109A (zh) * | 2010-09-30 | 2011-04-06 | 泰山医学院 | 基于氢为治疗物质的药物制剂及其制备方法 |
| WO2014079911A2 (en) * | 2012-11-21 | 2014-05-30 | Tata Steel Ijmuiden B.V. | Method for electrodeposition of chromium containing coatings from trivalent chromium based electrolytes |
| WO2017180587A2 (en) * | 2016-04-11 | 2017-10-19 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
| WO2018128167A1 (ja) * | 2017-01-06 | 2018-07-12 | 株式会社新菱 | 肌用シート |
| WO2018131505A1 (ja) * | 2017-01-11 | 2018-07-19 | 株式会社新菱 | 水素ガス含有ゲル、ならびにこれを含む食品および化粧料 |
| CN108779495A (zh) * | 2016-04-06 | 2018-11-09 | 雀巢产品技术援助有限公司 | 调节bckdh的方法 |
| CN109070037A (zh) * | 2016-04-14 | 2018-12-21 | 株式会社新菱 | 含气基材及其制造方法 |
| CN109292984A (zh) * | 2018-10-09 | 2019-02-01 | 浙江海洋大学 | 水产养殖用水质改良剂及其制备方法 |
| CN109350618A (zh) * | 2018-12-10 | 2019-02-19 | 山东农业大学 | 自噬调节剂在消除牛乳腺上皮细胞内金黄色葡萄球菌中的应用 |
| CN109674782A (zh) * | 2019-02-02 | 2019-04-26 | 山东农业大学 | 紫番茄花青素在调控铬诱导的lmh细胞自噬中的应用 |
| WO2019109168A1 (en) * | 2017-12-07 | 2019-06-13 | Teck Resources Limited | Process for treatment of mine impacted water |
-
2019
- 2019-08-19 CN CN201910763868.XA patent/CN110339205B/zh active Active
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1556795A (zh) * | 2001-09-21 | 2004-12-22 | 霍夫曼-拉罗奇有限公司 | 3－脱氧－维生素d3类似物酯 |
| CN101528691A (zh) * | 2006-08-22 | 2009-09-09 | 兰贝克赛实验室有限公司 | 基质金属蛋白酶抑制剂 |
| CN101138647A (zh) * | 2006-09-08 | 2008-03-12 | 远东纺织股份有限公司 | 制备覆膜基材用的组成物及覆膜基材的制法及其制品 |
| CN102000109A (zh) * | 2010-09-30 | 2011-04-06 | 泰山医学院 | 基于氢为治疗物质的药物制剂及其制备方法 |
| WO2014079911A2 (en) * | 2012-11-21 | 2014-05-30 | Tata Steel Ijmuiden B.V. | Method for electrodeposition of chromium containing coatings from trivalent chromium based electrolytes |
| CN108779495A (zh) * | 2016-04-06 | 2018-11-09 | 雀巢产品技术援助有限公司 | 调节bckdh的方法 |
| WO2017180587A2 (en) * | 2016-04-11 | 2017-10-19 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
| CN109070037A (zh) * | 2016-04-14 | 2018-12-21 | 株式会社新菱 | 含气基材及其制造方法 |
| WO2018128167A1 (ja) * | 2017-01-06 | 2018-07-12 | 株式会社新菱 | 肌用シート |
| WO2018131505A1 (ja) * | 2017-01-11 | 2018-07-19 | 株式会社新菱 | 水素ガス含有ゲル、ならびにこれを含む食品および化粧料 |
| WO2019109168A1 (en) * | 2017-12-07 | 2019-06-13 | Teck Resources Limited | Process for treatment of mine impacted water |
| CN109292984A (zh) * | 2018-10-09 | 2019-02-01 | 浙江海洋大学 | 水产养殖用水质改良剂及其制备方法 |
| CN109350618A (zh) * | 2018-12-10 | 2019-02-19 | 山东农业大学 | 自噬调节剂在消除牛乳腺上皮细胞内金黄色葡萄球菌中的应用 |
| CN109674782A (zh) * | 2019-02-02 | 2019-04-26 | 山东农业大学 | 紫番茄花青素在调控铬诱导的lmh细胞自噬中的应用 |
Non-Patent Citations (2)
| Title |
|---|
| PENG CHEN ET AL.: "The regulatory role of COX-2 in the interaction between Cr(VI)-induced endoplasmic reticulum stress and autophagy in DF-1 cells", 《ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY》 * |
| 陈鹏: "环氧合酶2(COX-2)对Cr(VI)致DF-1内质网自噬的调控研究", 《万方·学位论文》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114984046A (zh) * | 2022-05-05 | 2022-09-02 | 山东鑫谷健康产业有限公司 | 富氢水组合物及其在缓解动物温度应激中的应用 |
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