南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (2): 308-316.doi: 10.12122/j.issn.1673-4254.2023.02.21

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可诱导共刺激分子参与自发性高血压大鼠肠系膜血管内皮-间质转化及硬化

都昌乐，王 瑜 ，付计锋，曹冬黎，梅仁彪，张 奇   

  1. 安徽理工大学医学院机能学教研室，安徽 淮南 232001
  • 出版日期:2023-02-20 发布日期:2023-03-16

Inducible co-stimulatory molecules participate in mesenteric vascular endothelial-mesenchymal transition and sclerosis of mesenteric vessels in spontaneously hypertensive rats

DU Changle, WANG Yu, FU Jifeng, CAO Dongli, MEI Renbiao, ZHANG Qi   

  1. Department of Medical Functional Sciences, Medical College, Anhui University of Science and Technology, Huainan 232001, China
  • Online:2023-02-20 Published:2023-03-16

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摘要： 目的 探究可诱导共刺激分子（ICOS）与自发性高血压大鼠（SHR）肠系膜血管内皮-间质转化（EndMT）及硬化的相关性。方法 4周龄SHR大鼠（观察组）及同品系WKY大鼠（对照组）各20只，各组再随机分为4组，5只/组。无创血压测量仪动态监测各组大鼠血压情况，并于4、6、10、30周龄进行实验。采用流式细胞术检测大鼠脾脏CD4+T细胞的ICOS表达频数；RT-PCR法检测大鼠肠系膜中ICOS、VE-cad、α-SMA、Col3 mRNA表达；免疫组化技术检测大鼠肠系膜血管VE-cad、α-SMA、Col3及淋巴组织中ICOS、IL-17A、TGF-β的分布情况；ELISA法检测大鼠血浆中IL-17A、TGF-β含量水平；Masson染色观察大鼠肠系膜血管形态变化；Spearman和Pearson相关分析评价ICOS与VE-cad、α-SMA、Col3及胶原容积分数的相关性。结果 SHR大鼠自6周龄开始，与对照组相比收缩压增高（P<0.05）；CD4+T细胞ICOS的表达频数高于同期对照组（P<0.05）；肠系膜组织中ICOS、α-SMA、Col3、IL-17A和TGF-β的 mRNA及蛋白表达相较于对照组均升高（P<0.05），VE-cad mRNA及蛋白则在10周龄时表达下降（P<0.05）；自6周龄始SHR大鼠血浆中IL-17A、TGF-β含量水平提升（P<0.05）；肠系膜血管硬化程度不断加剧（P<0.05）；肠系膜组织中ICOS mRNA及蛋白表达水平与α-SMA、Col3表达水平和血管硬化程度自6周龄始均呈正相关（P<0.05），与VE-cad表达水平自10周龄始呈负相关（P<0.05）。结论 ICOS可能通过介导相关免疫反应在高血压肠系膜血管EndMT及硬化过程中发挥重要作用。

关键词: 可诱导共刺激分子；高血压；内皮-间质转化；血管硬化

Abstract: Objective To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR). Methods Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4+ T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-β in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-β in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis. Results Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4+ T cells at 6 weeks of age (P<0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-β in the mesentery were significantly higher than those in control group (P<0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P<0.05). The plasma levels of IL-17A and TGF-β were significantly increased in SHRs since 6 weeks of age (P<0.05) with progressive worsening of mesenteric vascular sclerosis (P<0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α- SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P<0.05) and a negative correlation with VE-cad expression level at 10 weeks (P<0.05). Conclusion ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.

Key words: inducible co-stimulatory molecules; hypertension; endothelial-mesenchymal transition; vascular sclerosis