细胞间粘附因子-1在高血压致炎症和心脏纤维化中作用的研究

目的探讨细胞间粘附因子-1(Intercellular Adhesion Molecular-1,ICAM-1)在高血压致炎症与心脏纤维化中的作用。方法将12只野生小鼠和12只ICAM-1敲除小鼠随机分成四组:野生对照组,野生血管紧张素Ⅱ灌泵组,ICAM-1敲除对照组,ICAM-1敲除血管紧张素Ⅱ灌泵组,给予血管紧张素Ⅱ(1500ng/kg*min,7d)及乙酸溶液(对照组)微量泵灌注,在灌注后第7天通过小鼠尾动脉套法测定各组血压,超声心动图检查以观察小鼠心脏结构和功能改变,马松染色、天狼星红染色观察心脏纤维化,免疫组化α-SMA染色观察肌成纤维细胞的形成,HE染色和免疫组化Mac-2、IL-1β、TGF-β染色观察炎症细胞浸润及炎症因子分泌。结果血管紧张素Ⅱ灌注第7天,灌泵组较对照组血压升高,说明造模成功。ICAM-1敲除灌泵组较野生灌泵组炎症细胞浸润增多(p<0.05n=6),尤其是Mac-2+巨噬细胞(p<0.05n=6),炎症因子TGF-β、IL-1β分泌增多(p<0.05n=6),α-SMA+肌成纤维细胞增多(p<0.05n=6)。结论在高血压致心脏纤维化过程中,ICAM-1敲除后,加重以Mac-2+巨噬细胞为主的炎症细胞浸润、增加炎症因子(TGF-β、IL-1β)分泌,导致心脏组织中α-SMA+的肌成纤维细胞形成,最终加重心脏纤维化。

The Role of Intercellular Adhesion Molecular-I in Angiotensin II Infusion-induced Cardiac Inflammation and Fibrosis

Objective To study the role of intercellular adhesion molecular（ICMA-1） in hypertension-induced cardiac inflammation and fibrosis. Methods Wildtype and ICAM-1 knockout mice were divided randomly into 4 groups （wildtype control group, 1CAM-1 knockout control group, wildtype angiotensin IIll infusion group, ICAM-1 knockout angiotensin II infusion group） with angiotensin II （1500ng/min＊kg, 7d） or solvent infusion （sham group） respectively. Mouse blood pressure was measured and echocardiography was performed at the 7th day of angiotensin II infusion. Results At the 7th day of angiotensin II infusion, the blood pressure of angiotensin II infusion group was higher than Sham group, and there was no difference in the wildtype and knockout group after angiotensin II infusion. The Masson Trichrome staining and Sirius-Red staining showed that ICAM-1 deficiency increased the angiotensin II infusion-induced cardiac fibrosis （p〈0.05 n=6）. Immunohistochemistry staining for a -SMA also showed that knockout of ICAM- 1 increased the a -SMA＋ myofibroblast formation. HE staining showed an increase in knockout mice in response to angiotensin II infusion. Compared with the angiotensin II infused wildtype group, ICAM-1 deficiency increased the Mac-2＋ macrophage infiltration into heart. Moreover, the inflammatory cytokines, including TGF- β and IL- 1 β, secretion was also increased by knockout of ICAM- 1 in response to angiotensin 1I infusion.Conclusion Our results demonstrate that ICAM-1 deficiency increased angiotensin II infusion induced inflammatory cells infiltration and inflammatory cytokines secretion, including TGF- β and IL-1β leading to a -SMA＋ myofibroblast formation, finally aggravated the cardiac fibrosis.