血钙水平与心血管疾病和癌症关系的研究进展

姚智昇，徐彦贵

(1.天津中医药大学 研究生院, 天津 300073; 2.天津市第一中心医院 药学部, 天津 300192)



短篇综述

血钙水平与心血管疾病和癌症关系的研究进展

姚智昇1，徐彦贵2*

(1.天津中医药大学 研究生院, 天津 300073; 2.天津市第一中心医院 药学部, 天津 300192)

血钙调节与许多疾病发生有一定关联。高血压及冠心病患者血钙水平低于健康人群，动脉粥样硬化患者钙积分大于健康人。不同癌症血钙水平呈现不同表现：肺癌、食管癌、胃癌血钙水平高于健康人；而结、直肠癌和乳腺癌低于健康人。补充钙剂可能对防病治病有一定作用。

血钙;高血压;冠心病;癌症

Ca2+参与肌细胞收缩、腺细胞分泌、囊胞中内容物释放、突触囊胞中递质释放及某些基质蛋白及酶蛋白激活等。Ca2+既是电流的载荷体又起信号分子作用，其作为第二信使与多种底物蛋白结合形成结合蛋白而发挥作用，本文综述血钙水平与心血管疾病及癌症关系的新进展。

1 血钙水平与心血管疾病

1.1 高血压

Ca2+与钙调蛋白结合并激活一氧化氮合酶(NOS),催化生成NO引起血管舒张，有报道韩国人高血压高发病率与高血浆钙水平负相关(调整风险比为1.24； 95%置信区间为1.07～1.43)，且高血钙水平对收缩压影响较舒张压更显著[1- 2]。高血压患者还伴有尿钙增加[3]，这对于肾结石合并高血压患者采取合理的治疗方案具有重要意义。维吾尔族原发性高血压患者血钙水平也低于维吾尔族正常对照组,且血钙水平每增加0.2 mmol/L,舒张压≥90 mmHg(1 mmHg=0.133 kPa) 的危险性降低0.42[4]，血钙水平对血管收缩的影响是通过Ca2+的调节机制实现。补充钙剂可降低高血压发病风险[5], 这对于高血压患者控制及合理选择降压药物具有重要的意义。

1.2 冠心病

高钙血症伴有冠心病的高发病率，冠状动脉钙化积分与血清钙水平明显相关,血清钙越高,冠状动脉钙化积分值越大,钙化积分值既是冠心病的诊断参数之一,也是冠心病治疗前后的观察指标及筛查隐匿性川崎病[6- 7]。腹部动脉钙化值有助于筛查梗阻性冠状动脉疾病，左心室向心性肥大就暗示有严重的潜在高血压、冠状动脉钙化的发生[8- 9]。颈动脉粥样硬化患者血钙水平显著高于健康人群[10]。颈动脉粥样硬化可能是钙盐沉积所导致，血钙水平是影响钙盐沉积的先决条件。

1.3 扩张型心肌病

婴儿扩张型心肌病伴有严重低血钙[11]。Ca2+与肌织网上的ryanodine受体结合,诱发肌质网释放Ca2+，激活平滑肌上钙调蛋白结合肌球蛋白轻链激酶,致肌球蛋白磷酸化和平滑肌收缩。

2 血钙水平与癌症

Ca2+作为第二信使参与凋亡早期信号传导, 破坏内环境稳态可直接引起线粒体释放色素C等促凋亡因子。肿瘤细胞无限增殖和改变细胞膜受体及离子通道功能表达的超敏性。而细胞分裂原诱导Ca2+内流,后者使细胞停止生长。血钙不足，降低Ca2+内流，减缓对细胞生长抑制。

2.1 肺癌

肺癌患者血钙水平较健康人增高[12],但伴骨转移肺癌患者与未伴有骨转移患者相比较,血钙值无明显差异。肺癌高钙血症发生率不高,发生率与骨转移无关,但临床中对于肺癌未伴骨转移患者也应警惕高钙血症发生。异硫氰酸烯丙酯刺激肺癌细胞诱导细胞内Ca2+浓度升高,而TRPA1(一种瞬间受体电位离子通道,激活后引起Ca2+通透入细胞内)拮抗剂可抑制Ca2+升高的效应[13]。在人类 SPC-AI肺腺癌细胞系中,通过L-型钙通道的Ca2+内流被证实与内皮素- 1有关，促进肿瘤增殖。Ca2+的内流可能促进内皮细胞释放VEGF/FGE和PDGF,以自分泌和旁分泌方式刺激血管生成。

2.2 乳腺癌

乳腺癌患者血浆中Ca2+、25-羟基维生素D、CaSR及E-cadherin水平均明显低于乳腺良性肿块组，提示血钙、25-羟维生素D、CaSR及E-cadherin与乳腺癌的发生有密切关系；原发性甲状旁腺功能亢进症和乳腺癌的风险之间的关联的报告显示高血钙的致病作用，而无甲状旁腺功能亢进症的高血钙水平与乳腺癌之间无关联，并且血钙水平与乳腺癌肿瘤大小和肿瘤发展阶段无关[14- 15]。增强质膜Ca2+结合ATP酶亚型4b的表达调节钙信号,可能有助于乳腺上皮细胞正常生长,也有可能诱导其癌变[16]。

2.3 其他癌症

肝癌细胞凋亡与Ca2+水平有相关性，甲基莲心碱诱导细胞凋亡期间，提高Ca2+水平均会增加凋亡蛋白表达，抑制环氧合酶- 2活性,达到治疗效果[17]。结、直肠癌患者血钙值低于健康人[18],每天摄入钙低于500 mg年轻妇女结直肠癌风险增加。补充钙提示可能预防肠癌。血清每增加0.1 mmol/L Ca2+，卵巢癌致命风险增高52%，如果是电离血清则会增高144%[19]。对化疗药物缺乏敏感性的癌细胞,Ca2+浓度呈现较高水平[20],Ca2+浓度升高可能与细胞自身侵袭性增加有关，血钙水平对化疗效果可能会有一定的协同作用。对于肾细胞癌高发性骨转移伴随着骨组织Ca2+浓度增高[21]。食管癌和胃癌血钙水平高于健康人，降低钙结合蛋白S100A14，胃癌肿瘤细胞未分化和不良预后增加[22- 23]。

T-型钙通道作为癌症治疗新途径[24]。在癌细胞中T-型钙通道异常表达或释放频繁发生，供给癌细胞增殖，对抗癌症治疗，T型钙通有可能作为治疗癌症的分子靶点，这为开发抗癌药物提供了新方向。此外，肿瘤细胞转移与细胞局部张力有关,张力激活钙通道是局部张力转化为钙信号的传导器。补充钙不能改善结、直肠癌和乳腺癌的治病风险和病死率，但可以降低前列腺癌的致病风险[25]。补充钙对其他癌症的影响还待进一步研究。

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Progress on the serum calcium level with cardiovascular disease and cancer

YAO Zhi-sheng1, XU Yan-gui2*

(1.Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300073;2.Dept. of Pharmacy,Tianjin First Central Hospital, Tianjin 300192,China)

Calcium regulation has some relationship with disease.The serum calcium level of patients with coronary heart disease and hypertension are lower that of than the healthy people. The calcium score of atherosclerosis is greater than healthy people. Different cancers show different performance levels of calcium: lung cancer, esophageal cancer and gastric cancer serum calcium levels higher than the healthy people; while the colorectal cancer and breast cancer is lower than that of healthy people. Taking calcium supplements may be helpful for some of diseases prevention and cure.

blood calcium; hypertension; coronary heart disease; cancer

2014- 09- 25

2015- 01- 22

1001-6325(2015)06-0851-03

R- 1

A

*通信作者(corresponding author)：13920455619@139.com