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2023年2月 第26卷 第5期 http: //www.chinagp.net E-mail: zgqkyx@chinagp.net.cn ·577·

investigated，however，studies on their role and mechanisms in hypertensive retinal disease are still lacking. Objective To
investigate the expression level of CaSR in hypertensive retina and its relationship with myocardial remodeling and retinal vascular
changes in hypertension. Methods Ten 8-week-old healthy wistar-kyoto rats （WKY） were selected as the WKY group，
and 20 homologous spontaneous hypertensive rats（SHR） of the same age were randomly divided into SHR group and inhibitor
（SHR+NPS2143） group from May to December 2021. During a 16-week intervention，the SHR+NPS2143 group received
intraperitoneal injection of CaSR inhibitor NPS2143，while WKY and SHR groups were intraperitoneally injected with the equal
volume of normal saline. At baseline and the end of intervention，blood pressure was measured by non-invasive blood pressure
monitor in all rats，and from each group，five rats were selected and executed，and myocardial and retinal tissues were taken out
for testing. Masson's Trichrome staining was used to measure the collagen deposition in the myocardium. H & E staining was used
to detect the pathological changes in retinal tissues. The distribution and expression of CaSR and vascular endothelial growth factor
A（VEGFA） in retinal tissues were detected using immunohistochemical staining and qRT-PCR. Results SHR group had
significantly higher levels of systolic blood pressure（SBP），diastolic blood pressure（DBP） and mean arterial pressure（MAP）
than WKY group either at baseline or the end of intervention（P<0.05）. SHR group had much lower levels of SBP，DBP and
MAP levels than SHR+NPS2143 group at the end of intervention（P<0.05）. At the end of the intervention，a significant growth
was found in SBP，DBP and MAP levels in both SHR and SHR+NPS2143 groups（P<0.05）. Compared with SHR group，
heart weight/body weight ratio（HW/BW%），left ventricle weight/body weight ratio（LVW/BW%），and myocardial collagen
volume fraction（CVF） were significantly decreased in WKY group but increased significantly in SHR+NPS2143 group（P<0.05）.
A significant growth was found in HW/BW%，LVW/BW% and CVF in both SHR and SHR+NPS2143 groups（P<0.05）. The
total retinal thickness and inner plexiform layer thickness were higher in SHR group than in WKY group at baseline and 16 weeks
of intervention（P<0.05）. The total retinal thickness and inner plexiform layer thickness were lower in the SHR group than in the
SHR+NPS2143 group at 16 weeks of intervention（P<0.05）. Compared with SHR group，the inner plexiform layer thickness at
16 weeks of intervention was decreased in WKY group and increased in SHR+NPS2143 group（P<0.05）. CaSR in the retina of
SHR group was lower than that of WKY group but higher than that of SHR+NPS2143 group（P<0.05）at 16 weeks of intervention.
VEGFA in the retina of SHR group was higher than that of WKY group but lower than that of SHR+NPS2143 group（P<0.05）at
16 weeks of intervention. Conclusion The use of CaSR inhibitor could reduce the activation of CaSR，increase the expression of
VEGFA in the retina，exacerbate hypertension-induced myocardial remodeling and the development of retinal vasculopathy.
【Key words】 Essential hypertension；Receptors，calcium-sensing；Vascular endothelial growth factor；Retinal
vessels；Myocardial remodeling；Rats

高血压是一种常见的心血管疾病，高血压的持续进 和 VEGF 受体 2（VEGFR-2）结合，影响血管通透性
展可引起心、脑、全身血管系统多个靶器官损害 ［1］ ， 和血管新生 ［9］ 。在多项研究中发现，CaSR 可与 VEGF
因此血压的监测对高血压的防控具有重要意义。视网膜 共同参与心血管疾病的发展 ［10-11］ 。故本研究通过探究
血管作为全身唯一可以直接通过肉眼观察的血管，关注 CaSR 在高血压大鼠心脏与视网膜血管中的作用，分析
其变化对高血压的进展评估具有一定的价值 ［2］ 。 CaSR 与 VEGF 在高血压视网膜血管病变中的关系，以
钙敏感受体（calcium-sensing receptor，CaSR）是 G 期对高血压及高血压靶器官损害的防治提供新思路。
蛋白偶联受体C家族的成员之一，存在于甲状旁腺、肾脏、 1 材料与方法
2+
肠道、骨骼等组织中 ［3］ ，在感知细胞外 Ca 和维持细胞 1.1 实验动物 本研究时间为 2021 年 5—12 月。从北
2+
内外 Ca 稳态的信号通路中起关键作用 ［4］ 。本课题组前 京维通利华实验动物有限责任公司购买（许可证编号：
期研究发现，CaSR 激动剂可有效降低血压，改善心肌重 SCXK 京 2021-0006）7 周龄清洁级健康雄性自发性高
塑 ［5］ 。2018 年 CaSR 首次在大鼠视网膜中被发现，并证 血压大鼠（spontaneously hypertensive rats，SHR）及同
明 CaSR 的表达降低与糖尿病视网膜病变发生有关 ［6］ ， 源相同周龄正常血压大鼠（wistar-kyoto rats，WKY），
但 CaSR 在高血压视网膜血管中的影响鲜见报道。 体质量约 180 g，饲养于石河子大学医学院动物房，普
血 管 内 皮 生 长 因 子（vascular endothelial growth 通饮食饲养，保证饲养环境安静整洁，避免嘈杂。实验
factor，VEGF）是诱导血管生成的重要细胞因子，与高 经石河子大学医学院第一附属医院医学伦理委员会批准
血压有着密切联系 ［7］ 。哺乳动物的 VEGF 家族由五种 （批准号：A2020-164-01）。
糖蛋白组成：VEGFA、VEGFB、VEGFC、VEGFD 和胎 1.2 主要试剂和仪器 NPS2143（美国 R&D 公司），
盘生长因子 ［8］ ，其中 VEGFA 是血管生成的关键媒介， CaSR 单克隆抗体（武汉三鹰公司），VEGFA 单克隆抗
通过与血管内皮细胞上表达的 VEGF 受体 1（VEGFR-1） 体（武汉博士德公司），苏木素 - 伊红（HE）染液（江