中国医药科学
中國醫藥科學
중국의약과학
CHINA MEDICINE AND PHARMACY
2013年
21期
19-23,43
,共6页
自发性高血压大鼠%心肌内小冠脉重构%巨噬细胞%肥大细胞%细胞间粘附分子-1%替米沙坦
自髮性高血壓大鼠%心肌內小冠脈重構%巨噬細胞%肥大細胞%細胞間粘附分子-1%替米沙坦
자발성고혈압대서%심기내소관맥중구%거서세포%비대세포%세포간점부분자-1%체미사탄
Spontaneously hypertensive rat%Intra myocardial small arteries remodeling%Macrophage%Mast cell%Intercellular adhesion molecule-1%Telmisartan
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。
目的：觀察自髮性高血壓大鼠（SHR）心肌內小冠脈重構（IMSAs）與巨噬細胞、肥大細胞及細胞間粘附分子-1（ICAM-1）的關繫，以及替米沙坦對血管重構及炎癥影響的榦預作用。方法12週齡的自髮性高血壓大鼠，隨機分為無榦預的SHR組（SHR）、高劑量替米沙坦組（Tel_H）和低劑量替米沙坦（Tel_L）組，對照組為週齡、性彆、體重配對的WKY大鼠（WKY），每組均為10隻；Tel_H組和Tel_L組每日分彆予替米沙坦8mg/kg、0.8mg/kg灌胃；SHR組和WKY組予2mL蒸餾水灌胃。實驗進行18週。實驗開始和結束時進行血壓測定。取大鼠左心室切片經苦味痠-天狼猩紅（Sirus-red）染色。利用計算機輔助成像繫統計算IMSAs的血管壁麵積（WA）、血管腔麵積（LA）和血管壁麵積百分比（%WA）。免疫組化染色以識彆巨噬細胞及細胞間粘附分子-1等。甲苯胺藍染色顯示心肌肥大細胞。結果30週齡時SHR組血壓（200.50±14.15）mm Hg比WKY組（116.30±9.38）mm Hg明顯升高，差異有統計學意義（P＜0.01）；Tel_H組血壓（119.40±14.69）mm Hg明顯低于SHR組（P＜0.01），而與WKY組差異無統計學意義（P＞0.05）；Tel_L組血壓（193.30±15.19）mm Hg與SHR組相比差異無統計學意義（P＞0.05）。SHR組IMSAs與WKY組IMSAs相比，WA及%WA顯著增高，LA明顯減小（P均＜0.01）；Tel_H組IMSAs與SHR組IMSAs相比，WA與%WA顯著減小（P＜0.01），而LA增大（P＜0.05）；Tel_H組與WKY組WA無顯著差異， LA減小（P＜0.05），而%WA增大（P＜0.01）。SHR組心肌組織中巨噬細胞和肥大細胞數量明顯多于WKY組（P均＜0.01）；Tel_H組和Tel_L組巨噬細胞和肥大細胞數量均顯著少于SHR組（P＜0.01）。SHR組心肌的ICAM-1光密度（IOD）顯著高于WKY組（P＜0.01），Tel_H組和Tel_L組心肌ICAM-1的IOD均顯著低于SHR組（P＜0.01）。結論30週齡SHR心肌內小冠脈重構與心肌組織中的巨噬細胞、肥大細胞數量及ICAM-1的錶達相關，替米沙坦治療能明顯減輕SHR心肌內小冠脈重構，減少心肌組織中的巨噬細胞、肥大細胞數量及ICAM-1的錶達。
목적：관찰자발성고혈압대서（SHR）심기내소관맥중구（IMSAs）여거서세포、비대세포급세포간점부분자-1（ICAM-1）적관계，이급체미사탄대혈관중구급염증영향적간예작용。방법12주령적자발성고혈압대서，수궤분위무간예적SHR조（SHR）、고제량체미사탄조（Tel_H）화저제량체미사탄（Tel_L）조，대조조위주령、성별、체중배대적WKY대서（WKY），매조균위10지；Tel_H조화Tel_L조매일분별여체미사탄8mg/kg、0.8mg/kg관위；SHR조화WKY조여2mL증류수관위。실험진행18주。실험개시화결속시진행혈압측정。취대서좌심실절편경고미산-천랑성홍（Sirus-red）염색。이용계산궤보조성상계통계산IMSAs적혈관벽면적（WA）、혈관강면적（LA）화혈관벽면적백분비（%WA）。면역조화염색이식별거서세포급세포간점부분자-1등。갑분알람염색현시심기비대세포。결과30주령시SHR조혈압（200.50±14.15）mm Hg비WKY조（116.30±9.38）mm Hg명현승고，차이유통계학의의（P＜0.01）；Tel_H조혈압（119.40±14.69）mm Hg명현저우SHR조（P＜0.01），이여WKY조차이무통계학의의（P＞0.05）；Tel_L조혈압（193.30±15.19）mm Hg여SHR조상비차이무통계학의의（P＞0.05）。SHR조IMSAs여WKY조IMSAs상비，WA급%WA현저증고，LA명현감소（P균＜0.01）；Tel_H조IMSAs여SHR조IMSAs상비，WA여%WA현저감소（P＜0.01），이LA증대（P＜0.05）；Tel_H조여WKY조WA무현저차이， LA감소（P＜0.05），이%WA증대（P＜0.01）。SHR조심기조직중거서세포화비대세포수량명현다우WKY조（P균＜0.01）；Tel_H조화Tel_L조거서세포화비대세포수량균현저소우SHR조（P＜0.01）。SHR조심기적ICAM-1광밀도（IOD）현저고우WKY조（P＜0.01），Tel_H조화Tel_L조심기ICAM-1적IOD균현저저우SHR조（P＜0.01）。결론30주령SHR심기내소관맥중구여심기조직중적거서세포、비대세포수량급ICAM-1적표체상관，체미사탄치료능명현감경SHR심기내소관맥중구，감소심기조직중적거서세포、비대세포수량급ICAM-1적표체。
Objective To investigate association of macrophages and mast cells and intercellular adhesion molecule-1 (ICAM-1) with remodeling of intra myocardial small arteries(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(Tel_H) 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 Tel_L 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 1eft 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. Macrophages and ICAM-1were demonstrated with immuno histochemistry staining. To luidine blue staining was performed to lable Mast cells. 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 Tel_L 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 cells 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-1 of Tel_H and Tel_L group were lessened (P<0.01, for each). Conclusion The amount of macrophages and mast cellsand the ICAM-1expressionin 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-1expressionin myocardial tissue.
