中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2009年
8期
685-691
,共7页
黄榕翀%姚康%陆浩%杨军%石洪成%章轶琦%黄浙勇%张书宁%杨珊%孙爱军%邹云增%葛均波
黃榕翀%姚康%陸浩%楊軍%石洪成%章軼琦%黃浙勇%張書寧%楊珊%孫愛軍%鄒雲增%葛均波
황용충%요강%륙호%양군%석홍성%장질기%황절용%장서저%양산%손애군%추운증%갈균파
心肌缺血%粒细胞集落刺激因子%心室功能%细胞凋亡
心肌缺血%粒細胞集落刺激因子%心室功能%細胞凋亡
심기결혈%립세포집락자격인자%심실공능%세포조망
Myocardial ischemia%Granulocyte colony-stimulating factor%Ventricular function%Apoptosis
目的 探讨冠状动脉内粒细胞集落刺激因子(G-CSF)注射治疗慢件缺血性心脏病猪的安全性和可行性.方法健康小型猪20只,成功建立慢性缺血性心脏病动物模型后4周,存活18只,随机分为对照组、G-CSF皮下注射组和G-CSF冠状动脉内注射组,每组6只.冠状动脉内注射组按照60μg/kg经冠状动脉内一次性给予G-CSF,皮下注射组按照5μg·kg-1·d-1连续5 d皮下注射G-CSF,对照组不做任何处理.于动物模型建立前、术后4周及8周分别行冠状动脉造影、99m Tc-甲氧基异丁基异腈(MIBI)/氟-18氟化去氧葡萄糖(18F-FDG)心肌双核素显像(DISA-SPECT)和首过延迟心肌灌注磁共振扣描(MRI),观察左心室射血分数(LVEF)、心肌损伤面积、心肌灌注面积及存活心肌的变化,并行血管、心肌病理学检查,观察新牛血管及心肌凋亡情况.结果冠状动脉内注射G-CSF后,慢性缺血性心脏病猪外周血G-CSF峰值时间为G-CSF动员后5 d,而皮下注射G-CSF峰值出现在动员后7 d,但两组间G-CSF峰值水平未见显著差别[(554.2±54.1)pg/ml比(590.8±87.9)pg/ml,P＞0.05].流式细胞分析显示,皮下注射途径和冠状动脉内注射G-CSF后,外周血 CD34+细胞比例与CD34+/CD133+细胞比例均明显高于对照组,但两组间差异无统计学意义.G-CSF皮下注射组和G-CSF冠状动脉内注射组靶病变血管远段狭窄程度均明显低于对照组(P均＜0.05),但两组间比较差异无统计学意义.MRI结果显示,G-CSF冠状动脉内注射组和G-CSF皮下注射组治疗4周后LVEF较动员前均明显改善(P＜0.01),G-CSF冠状动脉内注射组和G-CSF皮下注射组改善幅度均高于对照组(对照组比G-CSF皮下注射组比G-CSF冠状动脉内注射组:-2.5%±0.8%比5.8%±1.2%比5.0%±1.0%,与对照组比较P均＜0.01),但两种途径间差异无统计学意义.同时,G-CSF冠状动脉内注射组和G-CSF皮下注射组梗死心肌而积均显著减少,左心室重构均显著改善,存活心肌数量均显著增加,血管新生均增加,均抑制心肌细胞凋亡,两种途径问比较差异无统计学意义.结论经冠状动脉内注射G-CSF与皮下注射同样安全有效,可以改善慢性缺血性心脏病小型猪心脏功能.
目的 探討冠狀動脈內粒細胞集落刺激因子(G-CSF)註射治療慢件缺血性心髒病豬的安全性和可行性.方法健康小型豬20隻,成功建立慢性缺血性心髒病動物模型後4週,存活18隻,隨機分為對照組、G-CSF皮下註射組和G-CSF冠狀動脈內註射組,每組6隻.冠狀動脈內註射組按照60μg/kg經冠狀動脈內一次性給予G-CSF,皮下註射組按照5μg·kg-1·d-1連續5 d皮下註射G-CSF,對照組不做任何處理.于動物模型建立前、術後4週及8週分彆行冠狀動脈造影、99m Tc-甲氧基異丁基異腈(MIBI)/氟-18氟化去氧葡萄糖(18F-FDG)心肌雙覈素顯像(DISA-SPECT)和首過延遲心肌灌註磁共振釦描(MRI),觀察左心室射血分數(LVEF)、心肌損傷麵積、心肌灌註麵積及存活心肌的變化,併行血管、心肌病理學檢查,觀察新牛血管及心肌凋亡情況.結果冠狀動脈內註射G-CSF後,慢性缺血性心髒病豬外週血G-CSF峰值時間為G-CSF動員後5 d,而皮下註射G-CSF峰值齣現在動員後7 d,但兩組間G-CSF峰值水平未見顯著差彆[(554.2±54.1)pg/ml比(590.8±87.9)pg/ml,P＞0.05].流式細胞分析顯示,皮下註射途徑和冠狀動脈內註射G-CSF後,外週血 CD34+細胞比例與CD34+/CD133+細胞比例均明顯高于對照組,但兩組間差異無統計學意義.G-CSF皮下註射組和G-CSF冠狀動脈內註射組靶病變血管遠段狹窄程度均明顯低于對照組(P均＜0.05),但兩組間比較差異無統計學意義.MRI結果顯示,G-CSF冠狀動脈內註射組和G-CSF皮下註射組治療4週後LVEF較動員前均明顯改善(P＜0.01),G-CSF冠狀動脈內註射組和G-CSF皮下註射組改善幅度均高于對照組(對照組比G-CSF皮下註射組比G-CSF冠狀動脈內註射組:-2.5%±0.8%比5.8%±1.2%比5.0%±1.0%,與對照組比較P均＜0.01),但兩種途徑間差異無統計學意義.同時,G-CSF冠狀動脈內註射組和G-CSF皮下註射組梗死心肌而積均顯著減少,左心室重構均顯著改善,存活心肌數量均顯著增加,血管新生均增加,均抑製心肌細胞凋亡,兩種途徑問比較差異無統計學意義.結論經冠狀動脈內註射G-CSF與皮下註射同樣安全有效,可以改善慢性缺血性心髒病小型豬心髒功能.
목적 탐토관상동맥내립세포집락자격인자(G-CSF)주사치료만건결혈성심장병저적안전성화가행성.방법건강소형저20지,성공건립만성결혈성심장병동물모형후4주,존활18지,수궤분위대조조、G-CSF피하주사조화G-CSF관상동맥내주사조,매조6지.관상동맥내주사조안조60μg/kg경관상동맥내일차성급여G-CSF,피하주사조안조5μg·kg-1·d-1련속5 d피하주사G-CSF,대조조불주임하처리.우동물모형건립전、술후4주급8주분별행관상동맥조영、99m Tc-갑양기이정기이정(MIBI)/불-18불화거양포도당(18F-FDG)심기쌍핵소현상(DISA-SPECT)화수과연지심기관주자공진구묘(MRI),관찰좌심실사혈분수(LVEF)、심기손상면적、심기관주면적급존활심기적변화,병행혈관、심기병이학검사,관찰신우혈관급심기조망정황.결과관상동맥내주사G-CSF후,만성결혈성심장병저외주혈G-CSF봉치시간위G-CSF동원후5 d,이피하주사G-CSF봉치출현재동원후7 d,단량조간G-CSF봉치수평미견현저차별[(554.2±54.1)pg/ml비(590.8±87.9)pg/ml,P＞0.05].류식세포분석현시,피하주사도경화관상동맥내주사G-CSF후,외주혈 CD34+세포비례여CD34+/CD133+세포비례균명현고우대조조,단량조간차이무통계학의의.G-CSF피하주사조화G-CSF관상동맥내주사조파병변혈관원단협착정도균명현저우대조조(P균＜0.05),단량조간비교차이무통계학의의.MRI결과현시,G-CSF관상동맥내주사조화G-CSF피하주사조치료4주후LVEF교동원전균명현개선(P＜0.01),G-CSF관상동맥내주사조화G-CSF피하주사조개선폭도균고우대조조(대조조비G-CSF피하주사조비G-CSF관상동맥내주사조:-2.5%±0.8%비5.8%±1.2%비5.0%±1.0%,여대조조비교P균＜0.01),단량충도경간차이무통계학의의.동시,G-CSF관상동맥내주사조화G-CSF피하주사조경사심기이적균현저감소,좌심실중구균현저개선,존활심기수량균현저증가,혈관신생균증가,균억제심기세포조망,량충도경문비교차이무통계학의의.결론경관상동맥내주사G-CSF여피하주사동양안전유효,가이개선만성결혈성심장병소형저심장공능.
Objectives To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor ( G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia. Methods Eighteen Swine underwent placement of ameriod constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups ( n = 6 each) : ( 1 ) administration of vehicle (control) , (2) hypodermic injection of G-CSF(5 μg · kg-1·d-1 ) for five days (IH) , and (3) intracoronay injection of a bonus G-CSF (60 μg/kg) (IC). Coronary angiogram, cardiac MRI, and 18F-FDG-SPECT/99mTc-SPECT ( DISA-SPECT ) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diatolic volume ( LVEDV ) , left ventricular end-systolic volume ( LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR. Results MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronay injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis. Conclusions Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.
