CN114848621A - 赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途 - Google Patents
赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途 Download PDFInfo
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- CN114848621A CN114848621A CN202110156998.4A CN202110156998A CN114848621A CN 114848621 A CN114848621 A CN 114848621A CN 202110156998 A CN202110156998 A CN 202110156998A CN 114848621 A CN114848621 A CN 114848621A
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Abstract
本发明公开了赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途。赖氨酸可显著改善百草枯中毒引起的小鼠体重、饮食及饮水的减少，并改善小鼠中毒后肺纤维化与小鼠死亡，可用于百草枯中毒的治疗，缓解百草枯中毒后体内肺纤维化进展。
Description
技术领域
本发明涉及医药领域，具体涉及赖氨酸在制备用于抑制或治疗百草枯中毒致肺纤维化的药物中的用途。
背景技术
百草枯(paraquat,PQ)是目前广泛使用的有机杂环类接触性脱叶剂及除草剂，由于其获得途径极为方便，在临床上因误服或自服PQ发生中毒现象发生率较高，中毒后患者病死率极高。PQ中毒后可引起肺、肝、肾、脑等多器官损害，肺脏是其主要靶器官，进入机体后有90％蓄积于肺内，迅速破坏肺实质细胞，中毒早期可以引起广泛的肺出血及水肿，导致严重的急性肺损伤(acute lung injure,ALI)或急性呼吸窘迫综合症(actue respiratorydistress syndrome,ARDS)，甚至全身多脏器功能衰竭(multiple organ dysfunctionsyndrome,MODS)引起患者死亡，晚期则表现为进行性不可逆的肺间质纤维化，一旦出现肺间质纤维化，患者预后极差。目前临床上缺乏有效的治疗手段，没有特效解毒剂。
研究发现，PQ中毒后在肺组织内蓄积明显高于血浆，主要是因为在I型、Ⅱ型肺泡上皮细胞和Clara细胞膜上存在能够主动摄取PQ的多胺摄取系统。多胺是一类功能广泛的代谢调控物质，在细胞生长增殖、蛋白和核酸合成中具有重要作用。多胺摄取系统是生物体内用于调节多胺浓度并维持其动态平衡的一类能量依赖型的蛋白质介导系统，具有饱和状态，而PQ的化学结构与多胺类物质相近，故PQ可蓄积在肺内，对其产生严重损伤，最终导致肺纤维化。
临床上常将PQ根据程度中毒分为三种类型：(1)暴发型：PQ摄入量＞40mg/kg，伴严重的胃肠道症状，1～4天内死于多脏器衰竭，极少有存活者；(2)中到重型：PQ摄入量20～40mg/kg，除胃肠道症状外可出现多系统受累表现，数天至2周内出现肺部损伤，多数在2～3周后发生与ALI不相符的严重肺纤维化，死于呼吸衰竭；(3)轻型：PQ摄入量＜20mg/kg，除胃肠道症状外其他症状不明显，多数患者能够存活。既往研究认为PQ中毒损伤机制分以下几点：(1)活性氧自由基、NADPH耗竭、多不饱和脂肪酸氧化变性造成的细胞氧化损伤；(2)TNF-a、ILs、NF-kB等炎症因子对循环和代谢的影响，调节基因转录；(3)细胞内钙超载引起的一系列细胞分子生物学改变。但是PQ中毒后引起急性肺纤维化等一系列病理改变的相关的基因调节途径尚不明确，且治疗没有特效解毒剂，以对症支持治疗为主。大多数百草枯患者中毒后引起急性肺损伤或急性呼吸窘迫综合征，并最终死于肺纤维化。
由于百草枯中毒没有特效的解毒剂，其治疗仍处于探索阶段，目前主要疗法包括以下几个方面：
(1)减少毒物的吸收，促进毒物的排泄。完整的皮肤对PQ有屏障作用，因此，皮肤受污染应尽快脱去污染的衣物，用清水或弱碱性液体冲洗污染皮肤至少15min。百草枯中毒主要由消化道吸收引起，口服百草枯2h即可达血浆浓度高峰。因此洗胃应遵循早期、彻底、反复的原则。可用2％的碳酸氢钠溶液或质量分数为1％的皂土溶液；洗胃后胃管内注入漂白土或活性炭溶液以加强毒物的吸附，减少毒物经胃肠道吸收，也可同时注入硫酸镁或体积分数为20％的甘露醇溶液进行导泻。
(2)抗氧化治疗。维生素C、维生素E、谷胱甘肽的抗氧化作用已基本得到公认。有研究发现维生素C和药用炭有联合作用，能提高患者的救治成功率。N-乙酰半胱氨酸(NAC)是L-半胱氨酸的乙酰化衍生物，能提供大量的巯基。NAC在体内转化为半胱氨酸，能够促进谷胱甘肽合成并能直接清除自由基。实验证明，NAC能够抑制PQ通过氧化应激机制介导的肺泡细胞凋亡，并能通过推迟炎症反应发挥保护作用。硒是谷胱甘肽过氧化物酶和硫氧还蛋白还原酶保持生物活力所必需的微量元素。补充硒元素能减轻PQ诱导的GSH-PX和硫氧还蛋白还原酶活力的下降并能减轻PQ介导的细胞毒性作用。
(3)抗细胞因子治疗。乌司他丁是一种蛋白酶抑制剂，有很强的抑酶谱。研究发现，它能够同时抑制多重水解酶活性和炎症介质的释放。汉防己甲素(TET)对急性百草枯中毒大鼠血浆中SOD和GSH-PX活力降低有一定的拮抗作用。
(4)免疫抑制剂的治疗。研究表明使用环磷酰胺和加强龙单次和反复冲击治疗能有效阻止PQ中毒患者呼吸衰竭的发生，改善预后，降低病死率。激素还能提高机体对有害因子的耐受力，稳定溶酶体膜，减少炎症渗出，降低机体反应性，但常规剂量对PQ中毒效果并不明显，而激素(或加大用量)联合用药治疗效果明显。
(5)抗PQ抗体。目前PQ抗体主要用于测定组织中的百草枯浓度，其治疗价值仍处于探索阶段。国外学者尝试用抗PQ抗体(如抗PO—Fab片段或其他阻断剂)治疗PQ中毒，测定血液和组织中的PQ浓度，将PQ注入预先用PQ抗体处理的小鼠体内，发现血浆PQ浓度明显升高，尿中PQ排泄减少，PQ抗体可用于免疫治疗，分离血浆中的PQ，但不能阻止PQ在组织中的聚集。
(6)其他疗法：肺移植、低浓度氧疗等。
临床救治过程中应根据患者的情况选择合适的治疗方法，应早期，全方位，综合治疗。现在的很多研究，都是在没有特效解毒剂下所做的有益的探索，有待继续努力，寻找特效解毒剂和更经济的治疗方法，尽最大努力抢救患者，缓解症状，提高患者的治疗信心，提高生活质量。
赖氨酸(Lysine)是一种碱性必需氨基酸，机体不能自身合成，必须从食物中补充。赖氨酸已知在促进人体生长发育、增强机体免疫力、抗病毒、促进脂肪氧化、缓解焦虑情绪等方面都具有积极的营养学意义，同时也能促进某些营养素的吸收，能与一些营养素协同作用，更好的发挥各种营养素的生理功能。
赖氨酸在临床上已有成品用药，以盐酸赖氨酸形式存在，该药品分子量为182.65，主要用于治疗颅脑外伤、慢性脑组织缺血、缺氧性疾病的脑保护等。大鼠水平上，盐酸赖氨酸的口服半数致死量为10g/kg，腹腔注射半数致死量为4g/kg。盐酸赖氨酸的副作用较小，偶见轻度恶心、呕吐及过敏反应。已有研究分析了赖氨酸在灌流及透析过程中的清除情况，研究表明血液灌流、透析及两者联用并不显著影响赖氨酸的清除率，仅在透析过程中见赖氨酸浓度少量下降但无统计学意义。该研究说明赖氨酸与灌流/透析联用有其可行性，可用于相关疾病治疗。
有研究发现在百草枯中毒的大鼠模型中利用赖氨酸阿司匹林能在一定程度上缓解肺纤维化进展。在这些研究中，尽管药品名中存在赖氨酸，但研究并非关注赖氨酸的作用，而是聚焦阿司匹林在清除氧自由基中的作用，赖氨酸阿司匹林为阿司匹林的盐复合物，主要成分是阿司匹林，能溶于水，在体内存在时间很短，马上被血浆中的羧酸酯酶水解成水杨酸，在清除氧自由基及抗脂质过氧化等方面发挥作用。因此，上述研究并未涉及赖氨酸在百草枯中毒治疗中的作用，赖氨酸用于百草枯解毒的功能，这一发现截止目前尚未报道。
发明内容
本发明的目的是提供赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途。
为了达到上述目的，本发明提供了赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途。
本发明还提供了赖氨酸的在药学上可接受的盐在制备用于抑制或治疗百草枯中毒的药物中的用途。
优选地，所述抑制或治疗百草枯中毒是指缓解百草枯中毒后体内肺纤维化进展。
本发明还提供了一种用于抑制或治疗百草枯中毒的药物，其包含：赖氨酸或赖氨酸的在药学上可接受的盐，以及药学上可接受的载体或辅料。
相对于现有技术，本发明具有以下有益效果：
本发明提供了赖氨酸在治疗百草枯中毒的药物中的用途。发明人首次创新地研究发现百草枯能与富含赖氨酸基序的STIM1蛋白结合、活化下游NFAT家族并促进肺纤维化的分子机理，说明靶向STIM1赖氨酸基序可用于治疗百草枯中毒致肺纤维化及伴生多脏器衰竭的可能性。本发明发现赖氨酸显著改善百草枯中毒引起的小鼠体重、饮食及饮水的减少，并改善小鼠中毒后肺纤维化与小鼠死亡，赖氨酸可用于百草枯中毒的治疗。
附图说明
图1所示为赖氨酸抑制百草枯诱导的肺上皮细胞中NFAT活化。PQ，百草枯；Lysine，赖氨酸。其中***p<0.001，N.S.指无显著性差异，n＝3，p值经Two-Way ANOVA检验而得，p值小于0.001定义为***，以示百草枯引起的NFAT活化在赖氨酸共处理下受到抑制这一事件有显著性意义；n＝3表示该实验一组设计了3个重复孔。
图2所示为赖氨酸缓解百草枯引起的肺上皮细胞死亡。PQ，百草枯；Lysine，赖氨酸。其中***p<0.001，N.S.指无显著性差异，n＝3，p值经Two-Way ANOVA检验而得，p值小于0.001定义为***，以示百草枯引起的细胞死亡在赖氨酸共处理下受到抑制这一事件有显著性意义；n＝3表示该实验一组设计了3个重复孔。
图3至图9所示为赖氨酸改善百草枯急性中毒小鼠模型的症状。其中，
图3显示小鼠中毒后体重改变结果图，经连续观察4天统计体重丢失率。该结果表明赖氨酸显著抑制PQ中毒引起的小鼠体重丢失。其中*p<0.05，n＝10，p值经Two-Way ANOVA检验而得，p值小于0.05定义为*，以示百草枯引起的小鼠体重减轻在赖氨酸共处理下受到抑制这一事件有显著性意义；n＝10表示该实验一组设计了10只小鼠。
图4显示小鼠中毒后饮食量改变图，连续观察4天分别统计每天饮食量情况。该结果表明赖氨酸显著改善PQ中毒引起的小鼠饮食减少症状。其中*p<0.05，**p<0.01，n＝10，p值经Two-Way ANOVA检验而得，p值小于0.05定义为*，p值小于0.01定义为**，以示百草枯引起的小鼠饮食减少在赖氨酸共处理下得到改善这一事件有显著性意义；n＝10表示该实验一组设计了10只小鼠。
图5显示小鼠中毒后饮水量改变图，连续观察4天分别统计每天饮水量情况。该结果表明赖氨酸显著改善PQ中毒引起的小鼠饮水减少症状。其中*p<0.05，**p<0.01，n＝10，p值经Two-Way ANOVA检验而得，p值小于0.05定义为*，p值小于0.01定义为**，以示百草枯引起的小鼠饮水减少在赖氨酸共处理下得到改善这一事件有显著性意义；n＝10表示该实验一组设计了10只小鼠。
图6显示小鼠肺大体组织病变情况。图中显示百草枯中毒后小鼠肺组织发生实质病变，赖氨酸单处理小鼠肺组织无显著变化，百草枯与赖氨酸共处理组肺组织无明显实质病理改变。
图7显示小鼠肺组织羟脯氨酸累积情况，指示小鼠肺组织纤维化进展，羟脯氨酸累积越多纤维化越严重。图中显示每mg组织中羟脯氨酸累积情况。对照组(PBS)中百草枯中毒促进羟脯氨酸在肺组织中累积，实验组(赖氨酸)中羟脯氨酸在肺组织中的累积得到缓解。其中**p<0.01，***p<0.001，n＝7～10不等，p值经Two-Way ANOVA检验而得，p值小于0.01定义为**，p值小于0.001定义为***，以示百草枯引起的小鼠肺组织羟脯氨酸累积在赖氨酸共处理下得到改善这一事件有显著性意义；n表示该实验结果共显示n只小鼠结果(由于小鼠中毒死亡减少)。
图8显示小鼠肺病理组织切片形态及纤维化改变情况。HE，组织形态染色；Masson，组织纤维化染色，蓝色信号指示纤维化。该结果表明赖氨酸处理基本治愈百草枯中毒引起的小鼠肺纤维化。
图9显示小鼠中毒存活情况。黑色柱状图为百草枯单处理组，灰色柱状图为百草枯及赖氨酸共处理组。该结果记录小鼠截止处理4天时两组内小鼠存活情况。该结果表明百草枯中毒引起小鼠死亡(存活率70％)，赖氨酸与百草枯共处理小鼠未发生死亡(存活率100％)。
具体实施方式
以下结合附图和实施例对本发明的技术方案做进一步的说明。
术语“百草枯”，是一种速效触杀型灭生性联吡啶类除草剂，有效成分对叶绿体层膜破坏力极强，对非绿色组织没有作用，故具有很好的除草效果。
术语“肺纤维化”，指以成纤维细胞增殖及大量细胞外基质聚集并伴炎症损伤、组织结构破坏为特征的一大类肺疾病的终末期改变，也就是正常的肺泡组织被损坏后经过异常修复导致结构异常(疤痕形成)。肺纤维化严重影响人体呼吸功能，表现为干咳、进行性呼吸困难(自觉气不够用)，且随着病情和肺部损伤的加重，患者呼吸功能不断恶化。肺纤维化发病率和死亡率逐年增加，诊断后的平均生存期仅2.8年，死亡率高于大多数肿瘤，被称为一种“类肿瘤疾病”。
术语“STIM1”，指基质相互作用分子1(stromal interaction molecule 1)，其NCBI登录号为NP_001264890.1，该基因编码一种定位在内质网上的1型跨膜蛋白，在细胞内钙库Ca2+被消耗后通过调节钙库操纵的钙离子内流通道(store-operated Ca2+influxchannels，SOCs)介导钙离子内流。该基因的突变与致死性经典卡波西肉瘤、成纤维细胞中钙库操纵钙通道缺陷引起的免疫缺陷、外胚层发育不良和管状骨骼肌病有关。
术语“NFAT”，指活化T细胞核因子(nuclear factor of activated T cells)，其NCBI登录号为NP_001265598.1，该基因是一类转录因子家族，在免疫反应中对诱导基因转录起重要作用。除T细胞外，这类蛋白质还可以在许多免疫细胞上进行表达，如B淋巴细胞、肥大细胞、嗜酸性粒细胞等。其活性受到钙离子依赖性的钙调磷酸酶的调节。NFAT的功能主要为调节T细胞的活化，分化及自身耐受性，在机体免疫应答中诱导细胞因子及其他基因的转录等。
术语“赖氨酸”，指2，6-二氨基己酸，是一种碱性必需氨基酸。机体不能自身合成，必须从食物中补充。赖氨酸主要存在于动物性食物和豆类中，谷类食物中赖氨酸含量很低。赖氨酸在促进人体生长发育、增强机体免疫力、抗病毒、促进脂肪氧化、缓解焦虑情绪等方面都具有积极的营养学意义，同时也能促进某些营养素的吸收，能与一些营养素协同作用，更好的发挥各种营养素的生理功能。本发明所述“赖氨酸”可以是其本身，也可以是其衍生物。
术语“药学上可接受的盐”可以是有机酸盐和无机酸盐等。具体的有机酸盐可列举为甲酸盐、乙酸盐、酒石酸盐、枸橼酸盐、马来酸盐、富马酸盐、琥珀酸盐、草酸盐、苹果酸盐、乳酸盐、樟脑磺酸盐、柠檬酸盐；与低级烷基磺酸，如甲磺酸、乙磺酸、三氟甲磺酸等可形成甲磺酸盐、乙磺酸盐、三氟甲磺酸盐；与芳基磺酸，如苯磺酸或对甲苯磺酸等可形成对甲苯磺酸盐、苯磺酸盐；与氨基酸，如谷氨酸或天冬氨酸可形成谷氨酸盐或天冬氨酸盐。具体的无机酸盐为氢卤酸盐(包括氢氟酸、氢溴酸、氢碘酸、氢氯酸)、硫酸盐、磷酸盐、硝酸盐等。
发明人首次创新地研究发现百草枯能与富含赖氨酸基序的STIM1蛋白结合、活化下游NFAT家族并促进肺纤维化的分子机理，说明靶向STIM1赖氨酸基序可用于治疗百草枯中毒致肺纤维化及伴生多脏器衰竭的可能性。鉴于以上发现，发明人利用已有成品药物赖氨酸，发现赖氨酸能有效抑制百草枯诱导的NFAT活性，改善百草枯中毒引起的肺上皮细胞死亡，并呈现浓度梯度依赖性。同时，在百草枯中毒诱导的小鼠急性肺纤维化动物模型中的研究进一步发现，赖氨酸能治疗百草枯中毒引起的小鼠肺纤维化进展及伴生死亡。
本发明提供了赖氨酸在治疗百草枯中毒的药物中的用途。进一步地，包括赖氨酸在百草枯中毒致肺纤维化治疗中的应用，及赖氨酸在百草枯中毒致多脏器衰竭治疗中的应用。赖氨酸可用于制备抑制多因素引起的STIM1-NFAT活化及肺纤维化进展的药物。此外，用于治疗病毒感染、博来霉素、肿瘤放疗等所致的肺纤维化的药物也有望用于抑制STIM1-NFAT活化。
赖氨酸还可与其他药物活性成分联合制备药物，或者用于研究体外或体内抑制百草枯中毒致肺上皮细胞间质转换的用途。
实验1
赖氨酸抑制百草枯引起的NFAT活化。
A549肺上皮细胞接种于24孔板中，24小时贴壁后使用PolyjetTM转染试剂，根据制造商方案每孔转染0.5μg NFAT-luc及0.02μg Rennilla质粒。转染后细胞分别给与PBS或800μM(浓度)百草枯处理，同时根据培养基中赖氨酸浓度给与放大倍数的浓度梯度的赖氨酸处理(1倍、2.5倍、5倍)。处理24小时后，细胞以1X裂解缓冲液裂解，并根据制造商方案进行荧光素酶报告基因检测。
实验结果见图1。
图1：百草枯诱导肺上皮细胞中NFAT转录活性，赖氨酸抑制百草枯诱导的NFAT活化，并呈现浓度梯度依赖特征。
根据实验结果可见，赖氨酸具有抑制百草枯产生的毒性的作用，赖氨酸可用于治疗百草枯中毒。
实验2
赖氨酸抑制百草枯引起的肺上皮细胞死亡。
A549肺上皮细胞接种于96孔板中，24小时贴壁后细胞分别给与PBS或800μM百草枯处理，同时根据培养基中赖氨酸浓度给与放大倍数的浓度梯度的赖氨酸处理(1倍、2.5倍、5倍、10倍)。处理24小时后，细胞以SRB实验检测细胞活性。SRB实验具体流程如下：
1.每孔加入预冷三氯乙酸，使每孔终浓度为10％；
2.置4度孵育1小时；
3.去残液，96孔板流水冲洗5遍；
4.每孔加入50μl 0.4％的磺基罗丹明；
5.室温孵育10min；
6.每孔加入200μl 1％醋酸，洗3遍，风干；
7.每孔加入100μl Tris(10mM)溶解染料；
8.酶标仪检测，吸收光波长为515nM，读取OD值。
实验结果见图2。
图2：赖氨酸与百草枯共处理A549的结果，Ctrl为PBS处理组，PQ为百草枯处理组。
根据实验结果可见，赖氨酸能够抑制百草枯引起的细胞死亡，可用于治疗百草枯中毒。
实验3
赖氨酸抑制百草枯中毒引起的小鼠体重、饮食及饮水的减少，并改善百草枯中毒引起的肺纤维化与小鼠死亡。
6周龄C57/BL6小鼠置清洁级动物饲养笼中检疫与适应2周，确定合格后小鼠按体重平均分组，设立对照组(注射PBS或赖氨酸)和实验组(注射百草枯或共注射百草枯与赖氨酸)，每组设立10只小鼠。百草枯注射1次；赖氨酸每天注射1次，共注射3天。每天记录小鼠体重、每笼粮食及饮水重量，小鼠体重按“体重减轻率＝(初始值-观察时体重)/初始值”的公式计算小鼠每天体重减少情况；饮食饮水按“单只小鼠食水消耗量＝(前一天值-当天值)/小鼠数量”的公式计算每只小鼠平均饮食与饮水改变情况。第4天记录小鼠死亡情况并处死小鼠，分离肺大体组织，一部分经4％多聚甲醛固定后送公司进行组织病理分析，一部分用于羟脯氨酸的ELISA检测。
实验结果见图3至图9。
图3显示小鼠体重改变情况，实线为百草枯中毒组，虚线为百草枯中毒同时给与赖氨酸治疗组。实验结果可见赖氨酸显著抑制百草枯中毒引起的小鼠体重丢失。其中*p<0.05，n＝10，p值经Two-Way ANOVA检验而得；n＝10表示该实验一组设计了10只小鼠。
图4显示小鼠饮食改变情况，细虚线为百草枯中毒组，粗虚线为百草枯中毒同时给与赖氨酸治疗组。实验结果可见赖氨酸显著改善百草枯中毒引起的小鼠饮食减少症状。其中*p<0.05，**p<0.01，n＝10，p值经Two-Way ANOVA检验而得；n＝10表示该实验一组设计了10只小鼠。
图5显示小鼠中毒后饮水量改变情况，细虚线为百草枯中毒组，粗虚线为百草枯中毒同时给与赖氨酸治疗组。实验结果可见赖氨酸显著改善百草枯中毒引起的小鼠饮水减少症状。其中*p<0.05，**p<0.01，n＝10，p值经Two-Way ANOVA检验而得；n＝10表示该实验一组设计了10只小鼠。
图6显示小鼠肺大体组织病变情况。实验结果可见百草枯中毒后小鼠肺组织发生实质病变，赖氨酸单处理小鼠肺组织无显著变化，百草枯与赖氨酸共处理组肺组织无明显实质病理改变。
图7显示小鼠肺组织羟脯氨酸累积情况，指示小鼠肺组织纤维化进展，羟脯氨酸累积越多纤维化越严重。实验结果可见对照组(PBS)中百草枯中毒促进羟脯氨酸在肺组织中累积，实验组(赖氨酸)中羟脯氨酸在肺组织中的累积得到缓解。其中**p<0.01，***p<0.001，由于百草枯中毒引起死亡，n＝7～10不等，p值经Two-Way ANOVA检验而得。
图8显示小鼠肺病理组织切片形态及纤维化改变情况。HE，组织形态染色；Masson，组织纤维化染色，蓝色信号指示纤维化。实验结果可见赖氨酸处理基本治愈百草枯中毒引起的小鼠肺纤维化。
图9显示小鼠中毒存活情况。黑色柱状图为百草枯单处理组，灰色柱状图为百草枯及赖氨酸共处理组。该结果记录小鼠截止处理4天时两组内小鼠存活情况。实验结果可见百草枯中毒引起小鼠死亡(存活率70％)，赖氨酸与百草枯共处理小鼠未发生死亡(存活率100％)。
综上所述，本发明发现赖氨酸显著改善百草枯中毒引起的小鼠体重、饮食及饮水的减少，并改善小鼠中毒后肺纤维化与小鼠死亡，赖氨酸可用于百草枯中毒的治疗。
尽管本发明的内容已经通过上述优选实施例作了详细介绍，但应当认识到上述的描述不应被认为是对本发明的限制。在本领域技术人员阅读了上述内容后，对于本发明的多种修改和替代都将是显而易见的。因此，本发明的保护范围应由所附的权利要求来限定。
Claims (5)
1.赖氨酸在制备用于抑制或治疗百草枯中毒的药物中的用途。
2.根据权利要求1所述的用途，其特征在于，所述抑制或治疗百草枯中毒是指缓解百草枯中毒后体内肺纤维化进展。
3.赖氨酸的在药学上可接受的盐在制备用于抑制或治疗百草枯中毒的药物中的用途。
4.根据权利要求3所述的用途，其特征在于，所述的用途是指用于缓解百草枯中毒后体内肺纤维化进展。
5.一种用于抑制或治疗百草枯中毒的药物，其特征在于，包含：赖氨酸或赖氨酸的在药学上可接受的盐，以及药学上可接受的载体或辅料。
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Non-Patent Citations (3)
| Title |
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| RENATA SILVA等: "Several transport systems contribute to the intestinal uptake of Paraquat, modulating its cytotoxic effects", TOXICOLOGY LETTERS, vol. 232, no. 1, pages 271 - 283, XP029114431, DOI: 10.1016/j.toxlet.2014.10.015 * |
| XIUXIAN WAN等: "Metabolitic profiling of amino acids in paraquat-induced acute kidney injury", vol. 23, no. 4, pages 474 - 483, XP036741362, DOI: 10.1007/s10157-019-01702-z * |
| 兰敏;黄桂英;: "小儿厌食症应用小儿复方赖氨酸颗粒治疗的效果分析", no. 09, pages 83 - 84 * |
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