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Journal of Central South University Medical Sciences logoLink to Journal of Central South University Medical Sciences
. 2024 Mar 28;49(3):457–466. [Article in Chinese] doi: 10.11817/j.issn.1672-7347.2024.230497

心脏骤停后相关性贫血的机制及治疗

Mechanisms and treatment of anemia related to cardiac arrest

PENG Xiang 1,2, MO Xiaoye 1, LI Xiangmin 1,2,✉
Editor: 陈 丽文
PMCID: PMC11208403  PMID: 38970520

Abstract

Cardiac arrest is a common and fatal emergency situation. Recently, an increasing number of studies have shown that anemia in patients with cardiac arrest is closely related to high mortality rates and poor neurological outcomes. Anemia is prevalent among patients with post-cardiac arrest syndrome (PCAS), but its specific pathogenesis remains unclear. The mechanisms may involve various factors, including reduced production of erythropoietin, oxidative stress/inflammatory responses, gastrointestinal ischemic injury, hepcidin abnormalities, iatrogenic blood loss, and malnutrition. Measures to improve anemia related to cardiac arrest may include blood transfusions, administration of erythropoietin, anti-inflammation and antioxidant therapies, supplementation of hematopoietic materials, protection of gastrointestinal mucosa, and use of hepcidin antibodies and antagonists. Therefore, exploring the latest research progress on the mechanisms and treatment of anemia related to cardiac arrest is of significant guiding importance for improving secondary brain injury caused by anemia and the prognosis of patients with cardiac arrest.

Keywords: cardiac arrest, anemia, oxidative stress/inflammatory response, hepcidin, gastrointestinal ischemic injury

心脏骤停被定义为由于各种原因导致心脏射血突然停止，它具有体循环中断、呼吸停止和意识丧失的特征[1]。近年来，对心脏骤停患者的治疗和护理取得了长足的进步，但该类患者的预后仍然较差，住院生存率仅为28.7%[2-3]。贫血在危重病人中很常见，并常在重症监护病房(intensive care unit，ICU)住院的早期出现。但在心脏骤停后综合征(post-cardiac arrest syndrome，PCAS)患者中，贫血的发生率很少被报道。院内心脏骤停(in-hospital cardiac arrest，IHCA)后复苏的患者普遍存在贫血，IHCA患者的贫血患病率(90.8%)明显高于急性缺血性卒中(19.0%~43.0%)、急性冠脉综合征(10.0%~43.0%)和心力衰竭(42.6%)患者[4-7]。其原因可能涉及多种因素，如促红细胞生成素产生减少、氧化应激/炎症反应、胃肠道缺血性损伤、铁调素异常、医源性失血及营养不良[8]。虽然贫血在PACS患者中很常见，但该类患者对贫血的耐受性较差[9]。近来，研究[10]表明心脏骤停患者发生贫血与高病死率及神经功能预后差密切相关。因此，本文主要就心脏骤停后相关性贫血的危害性及其发病机制和治疗的研究进展进行概述，以期指导临床实践。

1. 心脏骤停后相关性贫血的危害性

美国心脏协会心肺复苏和急诊心血管护理指南等[11-13]推荐了改善心脏骤停预后的综合治疗策略，包括治疗性低温、经皮冠状动脉介入治疗、早期血流动力学优化和支持性护理。此类治疗的基本目标是通过维持氧气输送(oxygen delivery，DO2)和消耗之间的平衡来实现神经系统完整的生存，从而减轻缺血和缺氧对骤停后脑组织的影响。心脏骤停是一种严重的缺血事件，在缺乏适当的支持治疗的情况下，会导致器官防御机制失调。脑血管系统对缺氧的反应是通过增加一氧化氮的产生和刺激交感β2受体来实现足够的血管扩张，从而维持脑血流量[14-15]。然而，在严重贫血的情况下，这种脑血流量的增加仍不足以补偿由低血红蛋白(hemoglobin，Hb)水平引起的动脉氧含量的减少[16-17]。此外，与其他脑缺血事件相比，心脏骤停时，严重的低血压、心肌功能障碍和乳酸性酸中毒会使情况进一步复杂化，降低防御成功的概率。

Hb是动脉血氧含量的主要决定因素。早期心脏骤停后血流动力学管理的重点是维持DO2和消耗之间的适当平衡[18]。Hb在维持DO2中起着关键作用，贫血可能损害脑氧合，特别是在急性脑损伤后[19]。较低的Hb水平与急性缺血性卒中[20]、急性冠脉综合征[21]和心力衰竭[22]患者预后不良的风险增加有关。由于Hb是供氧的决定因素，心脏骤停患者可能对Hb水平降低和脑及其他缺血组织供氧减少更加敏感。此外，心脏骤停后心肌功能障碍很常见，这可能导致组织氧提取增加，从而降低混合静脉氧含量[23]。这可能会进一步降低动脉氧含量，而贫血可能会加重这一作用。因此，低Hb水平可能与PCAS患者的不良预后相关。近来，观察性研究[9, 24]表明，心肺复苏后或入院时的Hb水平与PCAS的临床结局相关。Johnson等[25]进行了一项包括598例患者的多中心观察性研究，发现预后良好的患者Hb水平显著升高。此外，多变量回归分析表明，较低的7 d平均Hb水平与不良结局相关。一项关于137例心脏骤停患者的回顾性研究[26]表明，较高的入院Hb水平是28 d神经系统预后良好的独立预测因子。以上研究均表明心脏骤停后患者对贫血的耐受性较差。重要的是，Ameloot等[27]在对82例患者的观察性研究中发现了Hb与脑氧合测量之间的联系。他们使用近红外光谱发现Hb与脑区域氧饱和度(regional cerebral oxygen saturation，rSO2)之间存在线性关联，Hb<100 g/L被确定为rSO2较低的临界值。此外，他们证实平均Hb水平<123 g/L特别是rSO2<62.5%的患者与神经系统预后较差相关。贫血与心脏骤停时引起的脑缺氧之间的联系及贫血对PCAS患者预后的影响需进一步的前瞻性研究进行探索。

2. 心脏骤停相关性贫血的发病机制

2.1. 促红细胞生成素产生减少且反应低下

促红细胞生成素(erythropoietin，EPO)是一种由肾脏产生的大小约30.4 kD(1 D=1 u)的糖蛋白。EPO对缺氧和贫血的反应快速且持续，健康人在急性缺氧刺激下2 h内EPO显著增加且直到刺激解除[28]。在低氧诱导的低氧诱导因子(hypoxia inducible factor，HIF)-1激活后，促红细胞生成素受体(erythropoietin receptors，EPORs)的表达增加。EPORs已在非造血组织中被发现，包括心肌、血管内皮、神经元和星形胶质细胞[29]。这些发现表明，EPO在心脏和大脑中起着组织保护细胞因子的作用，对于心脏骤停和心肺复苏(cardiopulmonary resuscitation，CPR)时无血流量或低血流量状态下的细胞保护非常有意义。

心脏骤停后机体呼吸、循环停止，全身组织严重缺血、缺氧，恢复自发性气胸循环(restoration of spontaneous circulation，ROSC)前存在的灌注衰竭和ROSC后再灌注时多种自由基和炎症细胞因子的大量释放[30]。有研究[31]表明心脏骤停后1 h，血液中细胞因子白细胞介素(interleukin，IL)-6和肿瘤坏死因子(tumor necrosis factor，TNF)-α会迅速升高，生存组IL-10水平明显下降。促炎细胞因子已被证明可以抑制EPO诱导的红细胞成熟和增殖，并降低相关的EPORs的表达[32]。炎症反应产生的细胞因子如IL-1、IL-6和TNF等会削弱EPO对缺氧的刺激性反应，从而使得红细胞合成减少，导致贫血的发生[33]。

2.2. 氧化应激/炎症反应

氧化应激/炎症反应在心脏骤停后相关性贫血的发病机制中起着重要作用。红细胞分布宽度(red cell distribution width，RDW)是衡量红细胞大小/体积变化的常规血液标志物，常结合其他指标用于血液系统疾病的识别和诊断[34]。最近，RDW已被用作评估危重症患者短期和长期病死率的预后指标。钟磊等[35]的研究表明，RDW升高是心脏骤停患者28 d和90 d全因病死率的独立预测因子。RDW的增加与炎症反应、氧化应激等多种因素有关[36]。研究[37]表明，氧化应激会导致红细胞膜损伤，RDW增加，循环红细胞半衰期缩短。Erol等[38]在PCAS死亡患者中观察到高RDW、低Hb、低血细胞比容和红细胞平均Hb水平。当PCAS患者出现全身炎症反应，氧化应激会降低红细胞存活率并影响骨髓功能，过早的红细胞生成导致RDW增加，同时外周循环释放增加。

同样，红细胞存活率的降低也可以通过溶血来解释，并导致Hb、血细胞比容和红细胞平均Hb水平的相应降低[39]。最近的研究[40]表明，在356名ROSC后第3天的幸存者中，28个(7.9%)样本检测到溶血。由ROS引起的氧化应激被认为在PCAS贫血的发生、进展和病理生理学中起着核心作用。这种氧化环境可以改变红细胞膜结构，导致红细胞功能受损，促进红细胞溶解，进而与内皮细胞结合，激活血小板和凝血因子，促进磷脂酰丝氨酸暴露和微泡释放[41]。心脏骤停后全身缺血再灌注引起的全身炎症和凝血功能障碍在缺氧脑损伤和多器官功能障碍中起重要作用。一旦发生心脏骤停，缺乏脉动性的血流会促进血块的快速形成，恢复自发性气胸循环后血块负荷将分布在整个血管系统和重要器官，产生弥散性血管内凝血[42]。有研究[43]认为，心脏骤停后中性粒细胞可通过释放大量氧自由基，导致血管内皮细胞严重受损，引起微血管通透性增加和血栓形成，使血管腔变窄，当红细胞通过时会发生不可逆的机械性损伤，从而引起机械损伤性溶血。

2.3. 胃肠道缺血性损伤

随着对PCAS的深入研究，研究人员发现经CPR后患者常发生早期胃肠功能障碍及肠系膜缺血和肠梗阻等病变，胃肠道作为人体最大的“细菌储存库”和“内毒素库”，是受PCAS影响最早和最严重的部位之一[44]。然而，由于诊断条件的限制，PCAS患者肠道损伤常被低估。关于肠道生物标志物瓜氨酸或肠脂肪酸结合蛋白(intestinal fatty acid binding protein，IFABP)的研究[45-47]表明，上消化道病变的高发体现了肠道对缺血再灌注损伤的易感性，几乎所有患者在院外心脏骤停(out-of-hospital cardiac arrest，OHCA)后都存在一定程度的肠道功能障碍。

L’Her等[48]的研究中，36例(26%)心脏骤停患者接受了肠内镜检查，且均观察到不同程度的肠道损伤，并有15例患者出现消化道出血，５例患者出现坏死性病变。此外，在另一项纳入69例CPR后患者的研究[45]中，82%的患者在入院时检测出IFABP水平升高，且在复苏24ｈ后82%的患者血浆瓜氨酸浓度降低，另外还有９例(13%)患者出现消化道出血。最近，Grimaldi等[49]通过对ICU住院期间的OHCA患者进行胃镜检查，发现在OHCA后成功复苏的患者中，超过55%的患者存在上消化道缺血性损伤。其中有一半有严重的病变(溃疡、坏死)，缺血性病变最常见的部位是胃底。因此，心脏骤停患者经常发生经胃肠道的临床上明显或隐蔽性失血，这也成为贫血的原因之一。

2.4. 铁调素异常

越来越多的人认识到，大多数危重症患者的贫血是铁利用不良的结果，类似于慢性病患者的贫血，目前将这类贫血称为炎症性贫血[50]。在这些患者中血清铁、血清转铁蛋白、转铁蛋白饱和度降低和铁蛋白水平升高，使骨髓造血细胞无法获得足够的原料，导致贫血。铁调素(hepcidin)是一种主要由肝细胞分泌的25氨基酸肽，目前被认为是铁稳态的主要调节因子[51]。血浆铁升高或细胞内铁超负荷、炎症等均可促进肝脏铁调素的表达，而红细胞生成的增加和低氧对铁调素表达的抑制，可增加铁向骨髓红细胞祖细胞的输送[52]。炎症细胞因子介导的铁调素升高是危重症患者贫血的重要介质，导致铁利用率低下。铁调素能下调小肠黏膜细胞和巨噬细胞膜的铁转运蛋白，抑制小肠铁吸收并减少巨噬细胞内Fe2+转运到血浆，降低血浆铁，减少红细胞的合成原料[53]。

Janus激酶2/信号转导与转录激活因子3(Janus kinase 2/signal transducer and activator of transcription 3，JAK2/STAT3)和铁调素调节蛋白(hemojuvelin，HJV)-骨形态发生蛋白(bone morphogenetic protein，BMP)-SMAD (small mother against decapentaplegic)蛋白是调控肝脏铁调素合成的2个信号通路[52, 54]。IL-6可通过JAK2/STAT3促进铁调素表达，铁调素与肝细胞膜IL-6受体结合后激活JAK1/2，使STAT3磷酸化，然后进入细胞核与铁调素基因启动子相应的位点结合，上调铁调素基因的表达；而IL-l、TNF-α等炎症因子则是先升高IL-6再作用于JAK2/STAT3[55]。在HJV-BMP/SMAD信号通路中的HJV是BMP的协同受体，HJV与Ⅰ型BMP受体结合后激活BMP，促进SMAD1/5/8磷酸化，磷酸化的SMAD与SMAD4形成复合体后进入细胞核，促进铁调素基因的表达[56]。铁调素与炎症因子的这种关系使PCAS患者血浆铁有被持续性下调趋势，从而导致慢性贫血。

2.5. 医源性失血及营养缺乏

PCAS患者抽血化验可及时而准确地监测和评估病情的变化，但频繁检测必然会丢失血液。最近研究[57]表明，静脉抽血仍然是危重病住院患者失血的主要来源，频繁的静脉抽血与Hb水平降低和输血率提高有关。ICU患者每次抽血量为(10.3±6.6) mL，24 h内为(41.1±39.7) mL[58]。虽然每次采血量较少，但累计血量则较大，且病情越重，采血越频繁[59]。故检验性失血是ICU患者贫血的主要原因之一。另外，PACS患者入住ICU后常由于血流动力学障碍，或行床旁血液净化，需行深静脉穿刺置管，若操作不熟练或拔除导管时未正确按压穿刺点也可因出现血肿等原因而失血。

重症患者常存在胃肠功能紊乱、营养物质吸收差等情况，加之机体处于高分解代谢状态，易出现铁、维生素B12及叶酸缺乏[60]，直接导致红细胞的合成原料减少。PACS患者入住ICU后大多无法正常进食，容易发生营养不良。同时，炎症可导致患者肠黏膜受损，营养素(尤其是铁)吸收减少。75%的ICU 危重症患者会发生缺铁[61]。另外，某些药物的使用，特别是抑酸药，亦可间接影响肠道铁的吸收。以上这些因素均可引起缺铁性贫血。

3. 心脏骤停后相关性贫血的治疗

3.1. 输血

输血阈值实践已在Hb<7 g/dL的危重症患者人群中进行了广泛研究，这被认为是非出血危重症患者的输血触发因素[62]。将ICU中的贫血患者输注到理想的目标Hb阈值是有害的，限制性输注政策可以带来更好的结果。然而，复苏指南并未建议PCAS患者的首选Hb水平或输血阈值。然而，输血是心脏骤停患者贫血的重要治疗手段，31%的患者由于各种原因至少接受过1次红细胞输注。在普通ICU、脓毒症甚至心脏病患者中，已采用较低的Hb阈值输血[63-64]。然而，这可能不适用于心脏骤停后复苏的患者，这些患者频繁的心肌功能障碍和伴随的严重脑损伤可能需要不同的输血策略。一项心肌缺血和输血(Myocardial Ischemia and Transfusion，MINT)试验[65]在急性心肌梗死患者中评估了限制性输血策略(Hb输血阈值为7~8 g/dL)是否不同于自由输血策略(Hb输血阈值<10 g/dL)。尽管各组在30 d复发性心肌梗死或死亡等主要复合结局方面没有明显差异，但自由输血在特定亚组中显示出优势，在1型心肌梗死患者中，限制性策略比自由策略导致更多的主要结局事件。研究[66]将Hb阈值9~10 g/dL作为骤停后护理的组成部分；另外，骤停后护理的组成部分还包括目标温度管理、血流动力学优化、呼吸机管理及血糖控制。Hb>10 g/dL与OHCA患者出院时良好的神经功能预后相关[67]。目前，在输血指南中没有关于PCAS的最佳Hb浓度或输血阈值的具体建议，还需进一步的随机对照实验来进一步研究。

3.2. 促红细胞生成药物

重组人促红细胞生成素(recombinant human erythropoietin，rhEPO)是一种造血生长因子，通过预防不同病理条件下的贫血以减少对临床输血的需求，并已被证明对人类是安全的，并广泛用于危重症患者[68]。然而，rhEPO的生物活性并不局限于调节红细胞生成。最近的一些实验研究[69-70]表明，rhEPO由于其抗凋亡的特性，在脑缺血和心脏缺血损伤动物模型中发挥神经保护作用和心脏保护作用，使其成为心脏骤停的潜在有用药物。在心肺复苏术中给予促红细胞生成素有助于提高ROSC发生率及ICU住院存活率[71]。在炎症性贫血小鼠模型中，中和抗体或铁调素小干扰RNA与rhEPO可通过减少铁调素纠正贫血[72]。虽然红细胞数量的增加和由此产生的氧输送增强在理论上可能有利于心脏骤停后的复苏，但药物作用通常会在用药后数天才出现，可能无助于心脏骤停。包含9项随机对照试验的荟萃分析[73]发现，接受促红细胞生成素治疗的危重症患者在总病死率、住院时间或机械通气持续时间方面没有任何差异。EPO组每例患者输血需要量减少0.4个单位，在使用促红细胞生成素来改善危重症患者的贫血方面，似乎没有任何明显的益处。Epo-ACR-02试验[74]表明，在疑似心脏原因的OHCA复苏的患者中，早期给予促红细胞生成素相比标准治疗并没有带来益处，而且与更高的并发症发生率相关，尤其是血栓性并发症。迄今，EPO对于心脏骤停的疗效在动物实验和临床应用上存在相互矛盾的结果。促红细胞生成素的作用可能因物种而异，动物实验和临床应用的时间窗也可能不同。

3.3. 抗炎/抗氧化治疗

分子氢是一种温和的抗氧化剂，可选择性地减少高活性氧化剂，如羟基自由基和过氧亚硝酸盐。分子氢具有多效性，包括抗炎和抗凋亡作用，以及缺血再灌注损伤后的抗氧化作用[75]。在心脏停搏动物模型中，分子氢能降低氧化应激和抗炎作用。近来，有研究表明吸入氢气能减轻PCAS患者的氧化应激水平[76]。乌司他丁具有抑制中性粒细胞弹性酶释放和抑制多种促炎细胞因子激活的作用，主要用于治疗胰腺炎、脓毒症、中毒性休克和失血性休克[77]。乌司他丁还能抑制ROSC后血清炎症因子的升高，Liu等[78]的研究发现乌司他丁可以降低TNF-α的表达，抑制IL-6的上调，因此使用乌司他丁可能会改善心脏骤停后贫血的发生。靶向目标温度管理是目前唯一经临床验证、可改善与PCAS相关的神经系统预后的治疗。靶向目标温度管理的神经保护机制包括氧化应激的衰减和抗炎作用[79]。一项多中心的随机对照试验研究[80]表明静脉注射高剂量的维生素C直接清除和减少心脏停搏后缺血/再灌注过程中有害活性氧的生成。以上措施对氧化应激/炎症反应引起的心脏骤停后相关性贫血均有潜在治疗作用。

3.4. 保护胃肠道黏膜

早期肠内营养支持可保护肠屏障的完整性，促进肠黏膜修复，增加营养物质吸收，改善患者的贫血。然而，针对诸如PCAS等血流动力学不稳定的患者，早期肠内营养(enteral nutrition，EN)的有效性和安全性尚不明确[81]。Grimaldi等[49]的研究表明心肺复苏期间使用较高的肾上腺素剂量是唯一与中重度缺血性病变相关的变量，而既往使用质子泵抑制剂和第1天血清碳酸氢盐与严重胃肠道缺血性损伤的发生率降低相关，提示心脏骤停前使用质子泵抑制剂具有保护作用，心脏骤停时胃pH值较低可能有利于缺血性病变的发展。心脏骤停后频繁发生肠道功能障碍及内窥镜下发现病变，提示临床上应对此类患者进行系统的胃肠道内窥镜检查；但根据医院资源的不同，很难对所有患者进行内镜检查，所以另一种方案是密切监测这些患者，预防性使用质子泵抑制剂治疗，并且仅对有出血证据的患者进行内窥镜检查。

3.5. 铁调素抗体及拮抗剂

3.5.1. HIF稳定剂

HIF是一种调节EPO合成并介导细胞适应缺氧的转录因子[82]。HIF可通过EPO介导的红细胞生成抑制铁调素表达，应用脯氨酸羟化抑制剂稳定HIF，促进内源性EPO产生，降低铁调素水平，增加肠道铁吸收及巨噬细胞释放贮存铁促进红细胞生成是治疗炎症性贫血的新兴策略[83-84]。

3.5.2. 靶向促炎因子-铁调素-膜铁转运蛋白轴治疗

“铁调素-膜铁转运蛋白轴”是调节人体铁代谢的关键信号通路。在感染、肿瘤、自身免疫等炎症状态下，IL-6与肝细胞表面的IL-6受体结合，通过JAK-STAT3途径刺激铁调素表达[85]。Kurzrock等[86]的研究报道Siltuximab(人-鼠嵌合的IL-6单克隆抗体)在Castleman病I期临床试验中明显降低铁调素水平，一半以上患者的贫血有所改善。新型治疗方法极具前景，靶向促炎因子-铁调素-膜铁转运蛋白轴治疗的安全性和有效性需进行大规模临床试验观察和证实。

3.6. 其他治疗

改善采血流程和设备可避免或减少抽血化验引起的失血。引进相关指南合理地指导抽血或尽可能降低检测所需的最低血量均可减少不必要的重复采血次数和采血量[87]。血液保存装置可在采血之初保存血液和采血之后回输多余血液，也能减少检验性失血[88]。此外，微量化学技术、更小试管(如儿科样管)及尽量一次抽血满足多个检查等均可减少检验性失血[89]。营养支持对心脏骤停后相关性贫血的治疗尤为重要，可补充红细胞生成所需的营养物质。连续性血液净化治疗已是治疗全身炎症反应综合征的常规方法，它能清除体内炎症介质，在理论上可消除炎症因子对铁调素和EPO的不利影响，从而改善心脏骤停后相关性贫血，但其疗效还需进一步临床验证。

4. 结 语

目前针对心脏骤停相关性贫血的研究较少，临床上PCAS患者贫血很常见且病因和发病机制均较复杂(图1)，而贫血直接影响患者的预后，增加病死率。我们应加强对心脏骤停相关性贫血的认识，采取综合措施予以避免或纠正，包括尽可能地减少医源性失血，避免红细胞生成所需营养物质的缺失，酌情补充铁剂和输血(表1)；但学术界对EPO的使用争议很大，尚需要进一步的临床研究。PCAS患者的铁代谢紊乱和由此引起的炎症相关性贫血机制和治疗均是其中的难点，需要深入研究。

图1.

图1

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心脏骤停后相关性贫血的发病机制

Figure 1 Mechanism of post-cardiac arrest related anemia IL: Interleukin; EPO: Erythropoientin; JAK2/STAT3: Janus kinase 2/signal transducer and activator of transcription 3; TNF-α: Tumor necrosis factor α; DIC: Diffuse intravascular coagulation.

表1.

心脏骤停相关性贫血机制及治疗的研究进展

Table 1 Research progress in mechanism and treatment of post-cardiac arrest related anemia

发病机制 治疗进展
促红细胞生成素产生减少且反应低下 采用促红细胞生成素，炎症因子抗体治疗
氧化应激/炎症反应 抗炎/抗氧化治疗，提高输血阈值
胃肠道缺血性损伤 早期予以肠内营养，质子泵抑制剂，内镜检查
铁调素异常

采用低氧诱导因子稳定剂

采用靶向促炎因子-铁调素-膜铁转运蛋白轴治疗
医源性失血及营养缺乏 改善采血流程和设备，采用微量化学技术，血液保存装置，补充造血原料
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基金资助

国家自然科学基金(82002010)。This work was supported by the National Natural Science Foundation of China (82002010).

利益冲突声明

作者声称无任何利益冲突。

作者贡献

彭祥 论文构思、撰写和修改；莫晓叶 对论文内容进行批评性审阅；李湘民 论文指导和终审。所有作者阅读并同意最终的文本。

Footnotes

http://dx.chinadoi.cn/10.11817/j.issn.1672-7347.2024.230497

原文网址

http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/202403457.pdf

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