趋化因子配体16在高盐诱导的盐敏感性高血压大鼠心肌重构中的作用  

The role of chemokine ligand 16 in high salt induced myocardial remodeling in salt sensitive hypertensive rats

作　　者：刘美丽[1,2] 宋海旭[1] 邵晓平 赵昕[1] 张效林[1] 田孝祥[1] 闫承慧[1] 韩雅玲[1] 

机构地区：[1]沈阳军区总医院心内科,沈阳110016 [2]大连医科大学临床医学院心血管内科,辽宁大连116044

出　　处：《解放军医学杂志》2015年第11期873-879,共7页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展计划(2012CB517804);国家自然科学基金青年项目(81500282);国家"十二五"重大新药创制研究项目(2012ZX09303016-002)~~

摘　　要：目的探讨趋化因子配体16(CXCL16)在高盐诱导的盐敏感性高血压大鼠心肌重构中的作用。方法 64只Dahl盐敏感大鼠按随机数字表随机分为正盐组及高盐组,每组32只。正盐组给予0.3%氯化钠饮食,高盐组给予8%氯化钠饮食;每周监测鼠尾血压。Western blotting检测正盐及高盐饮食2、4、6、8周大鼠心脏组织中CXCL16的表达;免疫荧光双染法确定CXCL16与心肌细胞及心肌成纤维细胞的共定位;免疫荧光及免疫组化染色观察6周和8周心脏组织中CXCL16及巨噬细胞标志物的表达变化; HE及Masson三原色法检测心脏纤维化情况。结果与正盐组相比,高盐组大鼠盐负荷1周起收缩压(147.10±3.67mm Hg vs 128.57±6.32mm Hg,P<0.01)、舒张压(110.86±4.24mm Hg vs90.69±4.51mm Hg,P<0.01)均有增高趋势。6周时高盐组大鼠心脏组织中CXCL16表达明显上调(1.18±0.05 vs0.58±0.02,P<0.05),8周时CXCL16的表达进一步增高(1.43±0.06 vs 0.67±0.03,P<0.05);8周时高盐组大鼠心脏出现明显纤维化重构,且巨噬细胞浸润明显增多。结论 CXCL16在高盐诱导的盐敏感性高血压心肌重构中表达增高,可能通过趋化巨噬细胞浸润参与了心肌纤维化病理过程。Objective To investigate the effects of chemokine ligand 16（CXCL16） in high salt induced myocardial remodeling in salt sensitive hypertensive rats. Methods Sixty-four Dahl salt sensitive（Dahl-SS） rats were randomly divided into normal salt（NS, 0.3% Na Cl） and high salt（HS, 8.0% Na Cl） group, 32 rats for each group. Blood pressure was measured by tailcuff method every week. Hearts were harvested and the expression of CXCL16 in heart tissues was detected by Western blotting at the 2nd, 4th, 6th and 8th week after NS or HS feeding. Immunofluorescence double staining was used to detect the colocalization of CXCL16 with both cardiomyocytes and cardiac fibroblasts. Immunofluorescence and immunohistochemical staining were used to detect the expression of CXCL16 and the biomarker of macrophage in the myocardial tissue after 6 week and 8 week of NS or HS feeding. Myocardial fibrosis was evaluated by HE and Masson trichrome staining. Results Compared with that in NS group, the systolic pressure and diastolic pressure in HS group increased significantly after 1 week of HS feeding（147.10±3.67 mm Hg vs128.57±6.32 mm Hg, P0.01 and 110.86±4.24 mm Hg vs 90.69±4.51 mm Hg, P0.01, respectively）. HS feeding significantly increased the myocardial CXCL16 expression in rats of HS group at the 6th week（1.18±0.05 vs 0.58±0.02, P0.05）, and the expression of CXCL16 was further up-regulated at the 8th week（1.43±0.06 vs 0.67±0.03, P0.05）. At the 8th week, obvious fibrosis remodeling and macrophage infiltration appeared in the myocardial tissue of the rats in HS group. Conclusion High salt intervention could up-regulate the expression of CXCL16 in salt sensitive hypertensive myocardial remodeling, which may promote macrophage infiltration and participate in the pathological process of myocardial fibrosis accordingly.

关 键 词：心室重构 趋化因子类 盐敏感性高血压 巨噬细胞 

分 类 号：R544.1[医药卫生—心血管疾病] R542.23[医药卫生—内科学]