Research Progress on Antihypertensive Effect of Polysaccharide and Its Mechanism
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摘要: 高血压是全球范围内导致残疾和过早死亡的主要风险因素之一，我国高血压及其相关并发症呈逐年升高的趋势，并逐渐年轻化。口服降压药虽能暂时将血压控制在一个正常范围内，但是可能会对机体多个系统产生严重的不良反应。随着多糖与高血压的关系研究逐渐深入，越来越多的研究表明多糖作为天然活性物质，对高血压具有安全、副作用小的优势。本文从多糖类别、来源、剂量、动物模型等方面介绍了多糖的降血压作用效果，阐述了多糖调节肾素-血管紧张素-醛固酮系统、改善内皮功能、调控多因子等降血压机制，简述了多糖与降血压作用的构效关系，对多糖应用于高血压的治疗前景进行了展望，为多糖降压药的研发提供了科学参考，也为高血压患者的疾病防治提供了更多的选择性。
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关键词:
- 多糖 /
- 高血压 /
- 降血压 /
- 作用机制 /
- 肾素-血管紧张素-醛固酮系统
Abstract: Hypertension is one of the major risk factors leading to premature death and disability worldwide. Hypertension and its related complications are increasing year by year in China, and tend to be younger nowdays. Blood pressure can be temporarily controlled within a normal range by oral antihypertensive drugs, but the serious adverse reactions maybe done to multiple systems of the body. With the in-depth research on the relationship between polysaccharides and hypertension, more and more results have shown that polysaccharides, as natural active substances, as safe for hypertension and have less side effects. This paper introduces the antihypertensive effect of polysaccharides from the aspects of type, source, dose and animal model of polysaccharides, and expounds the hypotensive mechanisms of polysaccharides, such as regulating renin-angiotensin-aldosterone system, improving endothelial function and regulating multi-factors. This paper briefly describes the structure-activity relationship between polysaccharides and antihypertensive effect, and looks forward to the prospect of polysaccharide application in the treatment of hypertension, which provides a scientific reference for the research and development of antihypertensive drugs of polysaccharides. It also provides more options for disease prevention and treatment of patients with hypertension. -
图 1 多糖降血压机制图
Figure 1. Diagram of the hypotensive mechanism of polysaccharides
注：Ang-Ⅰ：血管紧张素-Ⅰ（angiotensin-Ⅰ）；Ang-Ⅱ：血管紧张素-Ⅱ（angiotensin-Ⅱ）；ACE：血管紧张素转化酶（angiotensin converting enzyme）；RI：肾素抑制剂；ACEI：血管紧张素转化酶抑制剂（angiotensin converting enzyme inhibitior）；ARBs：血管紧张素受体阻滞剂（angiotensin receptor blockers）；RAS：肾素-血管紧张素系统（renin-angiotensin system）；AT1R：Ang-Ⅱ一型受体（angiotensin-Ⅱ type 1 receptor）；ET-1：内皮素-1（endothelin-1）；ETA：内皮素受体A（endothelin receptor A）；ETB：内皮素受体B（endothelin receptor B）；NOS；一氧化氮合酶（nitric oxide synthase）。
血压分级 收缩压（mmHg） 舒张压（mmHg） 正常 <120 <80 高血压前期 120~139 80~90 1期高血压 140~159 90~99 2期高血压 ≥160 ≥100 3期高血压 ≥180 ≥110 注：当收缩压与舒张压处于不同级别时，取较高的为准。 
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表 2 部分具有降血压作用的多糖及其作用效果
Table 2. Some polysaccharides with hypotensive effect and its effect
多糖
类别多糖来源 实验模型 多糖给药方式与剂量（mg/kg·d） 降压效果 参考文献 植物多糖 中草药 仙人掌果 A 灌胃：760、1580、2370 剂量依赖性降低血压，其中中、高剂量组降压
效果与卡托普利接近，无药物耐受现象且对
心率无影响[26-27] 中草药 天麻 B 灌胃：50、100、200 剂量依赖性降低血压，效果与卡托普利类似 [28] 中草药 黄芪 C 灌胃：400 显著降低血压并减缓高血压引发的血管和
肾脏损伤[29] 中草药 枸杞 B；D 灌胃：5、10、20、25 降低肾血管性高血压大鼠与妊娠期小鼠的血压，改善胎鼠发育 [30-31] 海洋植物 胶球藻 B 自由采食：50、100
（饲料中）可预防2K1C大鼠高血压的发生，显著降低血压 [32] 海洋植物 海带 B 灌胃：12.5、25、50 剂量依赖性降低血压，高剂量组与卡托普利效果相当，且作用平稳，对血管刺激小 [33] 海洋植物 海藻 G 口服（液体）：250、500 呈剂量依赖性降低血压，增加了钠排泄、
血清钠含量、血浆心钠素含量[34] 中草药配方 心肌尔康 B；E 细胞处理：0.15、0.3、0.6、1.2 mg/mL；灌胃：2470 剂量依赖性降低血压并减少高血压的损害 [35] 微生物多糖 真菌 白灵菇 A 灌胃：150 显著降低血压，可预防并改善高血压 [36] 细菌 开菲尔乳杆菌 F 灌胃：100、300 剂量依赖性显著降低血压 [37-38] 动物多糖 海洋动物 鱿鱼皮（硫酸化） H 体外试验：0.2~1.0 mg/mL 剂量依赖性抑制ACE活性 [39] 海洋动物 牡蛎多糖 H 体外试验：2.06 mg/mL 剂量依赖性抑制ACE活性 [40] 注：A：自发性高血压大鼠；B：两肾一夹（2K1C）诱导模型；C：血管紧张素-Ⅱ（angiotensin-Ⅱ，Ang-Ⅱ）诱导模型；D：冷刺激诱导模型；E：N-硝基-L-精氨酸甲酯（N-nitro-L-arginine methyl ester，L-NAME）诱导模型；F：易卒中自发性高血压大鼠；G：Sprague Dawley大鼠；H：体外试验；ACE：血管紧张素转换酶（angiotensin converting enzyme）。
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表 3 多糖对ACE活性的抑制效果
Table 3. Inhibitory effect of polysaccharide on ACE activity
多糖类别 多糖来源 剂量（mg/mL） ACE活性抑制率（%） IC50（mg/mL） 参考文献 植物多糖 杏仁副产品 5 79.5 2.81 [48] 植物多糖 开心果副产品 5 81.78 2.59 [48] 植物多糖 西瓜皮 1 93.93 0.21 [49] 植物多糖 海神草（硫酸化） 0.8 91.79 0.43 [50] 动物多糖 鱿鱼皮（硫酸化） 1 86.3 0.14 [39] 植物多糖 咖啡渣 0.6 H：86.95
U：98.17H：0.20
U：0.15[51] 植物多糖 鹰嘴豆多糖 1 87.83 / [52] 微生物
多糖乳酸菌胞外多糖 30 µL 15.82 3.66 [53] 动物多糖 牡蛎多糖 / / 2.06 [40] 植物多糖 红毛藻多糖 0~1000 / 0.34 [54] 注：IC50：半抑制浓度，即抑制一半ACE活性所需要多糖的浓度；H：热水处理法（hot water treatment）；U：超声波辅助法（ultrasound-assisted extraction）。
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表 4 多糖通过调控多因子降血压
Table 4. Polysaccharides lower blood pressure by regulating multiple factors
多糖
类别多糖
来源实验
模型多糖给药方式与剂量
（mg/kg·d）作用效果 作用机制 参考文献 植物多糖 中草药 仙人掌果 A 灌胃：760、1580、2370；灌胃：790、1580、3060 降压效果呈量效与
时效关系显著降低收缩压，降低血浆Ang-Ⅱ、ET水平，提升NO含量，保护主动脉内皮细胞，逆转血管平滑肌细胞增殖 [85-86] 中草药 黄芪 H 细胞处理：80、160、320 μg/mL 显著改善高血压血瘀症
患者症状可减轻高血压病患者内皮细胞的损伤，增强细胞活性和维持细胞形态结构 [22] 中草药 丹参 A 灌胃：40 显著降低收缩压与舒张压，降压效果与卡托普利相当 通过下调COX-2基因的表达，
显著降低血压，且降压效果与
卡托普利相近[89] 中草药 车前子（粗多糖） I 胶囊口服给药：1.6 g，每天2次 显著降低高血压患者血压 促进肠道双歧杆菌与多形拟杆菌的生长，改善肠道微生态 [23-24] 中草药 白桑果 A 细胞处理：0.5 mg/mL 显著下调自发性高血压大鼠与SD大鼠的血压 刺激内皮细胞产生NO，抑制ACE活性，诱导内皮依赖性舒张 [58, 90] 海洋植物 褐藻
（硫酸化）E 灌胃：1.6、3.1、6.2、12.5、25 降血压效果呈剂量依赖性 可能与促进体内NO生成或释放，降低ET-1和Ang-Ⅱ的水平有关 [87] 海洋植物 红藻
（硫酸化）J 自由采食：5% 显著降低血压，逆转大鼠
代谢综合征可通过减少炎性细胞对器官浸润以及发挥肠道益生功能改善代谢综合征 [91] 海洋植物 褐藻
（硫酸化）B 灌胃：12.5、25、50 呈剂量依赖性降低心率、动脉压、收缩压和舒张压 可能与促进体内NO生成，降低ET和Ang-Ⅱ释放有关 [88] 微生物
多糖真菌、
中草药冬虫夏草 A 灌胃：50、100、200 降血压效果呈时间与剂量依赖性，中剂量多糖可使肾Ang-Ⅱ恢复至正常水平 促进NO的分泌，降低血浆ET-1
与Ang-Ⅱ的水平，降低C反应
蛋白表达[84] 注：A：自发性高血压大鼠模型；B：两肾一夹（2K1C）诱导模型；E：左侧肾动脉缩窄诱导模型；H：自发性高血压患者；I：老年高血压患者；J：高碳水化合物、高脂肪诱导模型；ACE：血管紧张素转换酶（angiotensin converting enzyme）；Ang-II：血管紧张素-Ⅱ（angiotensin-Ⅱ）；ET：内皮素（endothelin）；NO：一氧化氮（nitric oxide）；ET-1；内皮素-1（endothelin-1）。
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