自发性高血压大鼠心肌内小冠脉重构与炎症关系的观察

Association of inflammation with remodeling of intramyocardial small arteries in spontaneouslyhypertensive rats

目的观察自发性高血压大鼠(SHR)心肌内小冠脉重构(IMSAs)与巨噬细胞、肥大细胞及细胞间粘附分子-1(ICAM-1)的关系,以及替米沙坦对血管重构及炎症影响的干预作用。方法 12周龄的自发性高血压大鼠,随机分为无干预的SHR组(SHR)、高剂量替米沙坦组(Tel_H)和低剂量替米沙坦(Tel_L)组,对照组为周龄、性别、体重配对的WKY大鼠(WKY),每组均为10只;Tel_H组和Tel_L组每日分别予替米沙坦8mg/kg、0.8mg/kg灌胃;SHR组和WKY组予2mL蒸馏水灌胃。实验进行18周。实验开始和结束时进行血压测定。取大鼠左心室切片经苦味酸-天狼猩红(Sirus-red)染色。利用计算机辅助成像系统计算IMSAs的血管壁面积(WA)、血管腔面积(LA)和血管壁面积百分比(%WA)。免疫组化染色以识别巨噬细胞及细胞间粘附分子-1等。甲苯胺蓝染色显示心肌肥大细胞。结果 30周龄时SHR组血压(200.50±14.15)mm Hg比WKY组(116.30±9.38)mm Hg明显升高,差异有统计学意义(P<0.01);Tel_H组血压(119.40±14.69)mm Hg明显低于SHR组(P<0.01),而与WKY组差异无统计学意义(P>0.05);Tel_L组血压(193.30±15.19)mm Hg与SHR组相比差异无统计学意义(P>0.05)。SHR组IMSAs与WKY组IMSAs相比,WA及%WA显著增高,LA明显减小(P均<0.01);Tel_H组IMSAs与SHR组IMSAs相比,WA与%WA显著减小(P<0.01),而LA增大(P<0.05);Tel_H组与WKY组WA无显著差异,LA减小(P<0.05),而%WA增大(P<0.01)。SHR组心肌组织中巨噬细胞和肥大细胞数量明显多于WKY组(P均<0.01);Tel_H组和Tel_L组巨噬细胞和肥大细胞数量均显著少于SHR组(P<0.01)。SHR组心肌的ICAM-1光密度(IOD)显著高于WKY组(P<0.01),Tel_H组和Tel_L组心肌ICAM-1的IOD均显著低于SHR组(P<0.01)。结论 30周龄SHR心肌内小冠脉重构与心肌组织中的巨噬细胞、肥大细胞数量及ICAM-1的表达相关,替米沙坦治疗能明显减轻SHR心肌内小冠脉重构,减少心肌组织中的巨噬细胞、肥大细胞数量及ICAM-1的表达。

Objective To investigate association of macrophages and mast cells and intercellular adhesion molecule-1 （ICAM-1） with remodeling of intra myocardial small artcries（IMSAs） in spontaneously hypertensive rats, and toobserve the effects of telmisartan. Methods 12-week-oldmale SHRs were randomized to 3 groups, including non-treated SHR group, telmisartan high dose（TelH） group, telmisartanlow dose（Tel L）group.Age and sex and weight matched Wistar Kyoto rats were control group （WKY, n=10）. Rats in Tel_H group and TelL group received telmisartan 8mg/（kg ~ d）, 0.8mg/（kg ~ d） by intragastric administration respectively. Experiments were continued for 18 weeks.The blood pressure of all theanimals was measured at the beginning and at the end of experiment, and then, all animals were sacrificed. The left ventricle tissue sections were stained with Sirus-red, for morphological evaluation of IMSAs. The wall area, lumen area and percent wall area of IMSAs were assessed with thecomputer-assisted image analysis system. Maerophages and lCAM-lwere demonstrated with immuno histochemistry staining. To luidine blue staining was performed to lable Mast ceils. Results Systolic blood pressure （SBP） in SHR group at week 30 was significantly higher than those in WKY group（200.50-＋ 14.15）mmHg vs （116.30-＋ 9.38）mm Hg, P 〈 0.01）. SBP in Tel_H group （119.40 ＋ 14.69） mm Hg was significantly lower than those in SHR group, but was no significant difference with those in WKY group. There＇s no significant difference in SBP between Tel_L group （193.30 ＋ 15.19） mm Hg and SHR group. WALL AREA and %WALL AREA of IMSAs were increased and LA wall areas decreased in SHR group, compared with WKY group （P 〈 0.01 for each）. Wall area and percent wall areain Tel_H group were lower than SHR group, but lumen areas were greater （P 〈 0.01 for each）. Wall area and percent wall area were reduced in TelL group,compared with SHR group （P 〈 0.05 for each）, but lumen area were no difference between both groups.The amount of macrophages and mast cells in leftventricle of SHR group were great increased, compared to WKY group （P 〈 0.01 for each）. The count of macrophages and mast ceils in left ventricle ofboth Tel_H and Tel Lwere markedly lower than those in SHR group （P 〈 0.01 for each）. The IOD of ICAM-1 in left ventricle of SHR group were remarkedly higher than those of WKY group （P 〈 0.01）. Compared with SHR group, the IOD of ICAM-I of Tel_H and TeI_L group were lessened （P 〈 0.01, for each）. Conclusion The amount of macrophages and mast cellsand the ICAM-lexpressionin myocardial tissuemay associate with remodeling of intra myocardial small arteries in 30-week-old SHRs. Telmisartan reduced remodeling of intra myocardial small arteries in SHRs, and reduced the amount of macrophages, mast cells and the ICAM-lexpressionin myocardial tissue.