CTRP2与冠状动脉阻塞患者侧支循环形成的临床关联及相关作用

doi:10.3969/j.issn.1674-8115.2021.07.011

摘要/Abstract

摘要：

目的·探讨C1q肿瘤坏死因子相关蛋白2（C1q/tumor necrosis factor-related protein-2，CTRP2）与冠状动脉阻塞患者侧支循环形成的关联及其作用。方法·选取2019年9月—12月在上海交通大学医学院附属瑞金医院心内科住院并进行冠状动脉造影确诊为冠状动脉阻塞的患者177人，根据Rentrop分级标准，以患者冠状动脉侧支循环情况分级为侧支循环形成不良组和侧支循环形成良好组，采用酶联免疫吸附测定（enzyme linked immunosorbent assay，ELISA）检测患者血浆中脂肪因子补体CTRP2表达水平。构建下肢缺血动物模型，分为对照组和CTRP2过表达组，通过激光多普勒仪测定血供恢复情况，计算血供恢复比率。使用重组CTRP2蛋白以50、100及200 pg/mL的剂量刺激血管内皮细胞，于Matrix Gel上检测血管环形成能力，并通过Transwell检测内皮细胞迁移能力。结果·临床研究发现冠状动脉阻塞患者中侧支循环形成良好患者相较于侧支循环形成不良患者血浆CTRP2水平升高（P=0.009），CTRP2对侧支循环形成不良的风险比OR=0.889，95% CI 0.844~0.936，P=0.000。动物模型研究发现CTRP2可促进小鼠下肢缺血模型血供恢复（P=0.032，P=0.009）。细胞实验发现CTRP2增强内皮细胞成血管和迁移能力，且与其浓度呈正相关（均P<0.05）。结论·冠状动脉阻塞患者中侧支循环形成良好患者血浆CTRP2表达水平升高，CTRP2可促进动物体内侧支循环的建立及体外内皮细胞成血管和迁移。

关键词: CTRP2, 冠状动脉阻塞, 侧支循环, 血管新生

Abstract:

Objective·To explore the relationship between C1q/tumor necrosis factor-related protein-2 (CTRP2) and collateral circulation in patients with coronary artery occlusion.

Methods·Firstly, 177 patients who were hospitalized in the Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2019 to December 2019 and were diagnosed with coronary artery obstruction by coronary angiography were selected. According to the Rentrop method, the patients were classified into two groups: poor collateral circulation formation group and good collateral circulation formation group. ELISA was used to detect the level of adipokine complement CTRP2 in patients′ plasma. The animal model of lower limb ischemia was established and divided into contrast group and CTRP2 overexpression group. The recovery of blood supply was measured by laser Doppler instrument and the recovery ratio of blood supply was calculated. Finally, the recombinant CTRP2 protein was used to stimulate vascular endothelial cells at the doses of 50, 100 and 200 pg/mL, and the percentage was detected on Matrix Gel. The migration ability of endothelial cells was detected by Trans-well.

Results·Clinical study found that the plasma CTRP2 level in patients having coronary artery occlusion with good collateral formation was higher than that in patients with poor collateral circulation (P=0.009), and the risk ratio of CTRP2 to poor collateral circulation was OR=0.889, 95%CI 0.844?0.936, P=0.000. The animal model study found that CTRP2 can promote the recovery of blood supply in mice with lower limb ischemia (P=0.032, P=0.009). Cell experiments showed that CTRP2 enhanced the angiogenesis and migration ability of endothelial cells, and it was positively correlated with its concentration (all P<0.05).

Conclusion·The level of plasma CTRP2 in patients having coronary artery occlusion with good collateral circulation is increased. CTRP2 can promote the establishment of collateral circulation in vivo and the angiogenesis and migration of endothelial cells in vitro.

Key words: C1q/tumor necrosis factor-related protein-2 (CTRP2), coronary occlusion, collateral circulation, angiogenesis

中图分类号:

R541.4

汤静, 于晨溪, 陈中丽, 章安迪. CTRP2与冠状动脉阻塞患者侧支循环形成的临床关联及相关作用[J]. 上海交通大学学报(医学版), 2021, 41(7): 915-919.

Jing TANG, Chen-xi YU, Zhong-li CHEN, An-di ZHANG. Relationship between CTRP2 and coronary collateral circulation[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(7): 915-919.

图/表 4

表1 研究对象的临床特征

Tab 1 Clinical features of the study population

Item	Poor collateral growth （n=89）	Good collateral growth （n=88）	P value
Age/year	61.0±1.5	61.0±0.9	0.743
Male/n（%）	62 （69.7）	59 （67.0）	0.832
Body mass index/（kg·m^-2）	24.3±0.7	24.5 ±0.9	0.233
Hypertension/n（%）	52 （58.4）	48 （54.5）	0.712
Diabetes/n（%）	24 （27.0）	21 （23.9）	0.763
Family history of coronary heart disease/n（%）	16 （18.0）	13 （14.8）	0.783
Smoking/n（%）	23 （25.8）	29 （32.9）	0.382
Drinking/n（%）	18 （20.2）	22 （25.0）	0.562
Acute coronary syndrome/n（%）	11 （12.4）	14 （15.9）	0.644

图1 CTRP2在不同侧支循环冠状动脉阻塞患者中的表达含量

Fig 1 Expression level of CTRP2 in patients having coronary artery obstruction with different collateral growth

图2 CTRP2对于小鼠下肢缺血模型血供恢复作用Note： A. Laser Doppler detection results of the blood supply of mice before the surgery of femoral artery ligation, immediately after surgery and 21 d after surgery. B. The detection results of the blood flow recovery rate before the operation of femoral artery ligation, immediately after the operation and 7 d, 14 d and 21 d after the operation. Among them, 6 mice were injected with negative control lentivirus as the control group and 6 mice were injected with lentivirus overexpressing of CTRP2 as the CTRP2(+) group. ①P=0.032, ②P=0.009, compared with the control group.

Fig 2 Effect of CTRP2 on blood supply restoration in the mouse model of lower limb ischemia

图3 CTRP2对于血管内皮细胞功能的影响Note： A. After endothelial cells were stimulated with different concentrations of CTRP2 (50, 100 and 200 pg/mL) for 8 h, the ability of vascular ring formation was detected on Matrix Gel and the ability of endothelial cell migration was detected by Transwell (×8). The group without the stimulation of CTRP2 was regarded as the normal control group. B. The results of the circumference of vascular rings. ①P=0.031, ②P=0.009, ③P=0.001, compared with the control group. C. The results of Transwell staining. ④P=0.024, ⑤P=0.003, ⑥P=0.001, compared with the control group.

Fig 3 Effect of CTRP2 on the function of vascular endothelial cells

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