中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2011年
2期
176-180
,共5页
邢晓倩%徐健%苏浩%卢业伟
邢曉倩%徐健%囌浩%盧業偉
형효천%서건%소호%로업위
心房颤动%心脏起搏,人工%心肌%连接蛋白类
心房顫動%心髒起搏,人工%心肌%連接蛋白類
심방전동%심장기박,인공%심기%련접단백류
Atrial fibrillation%Cardiac pacing,artificial%Myocardium%Connexins
目的 心房颤动(房颤)的发生及维持机制与心房结构重构和电重构有关.缝隙连接蛋白(connexin,Cx)是心肌闰盘的重要组成结构.一旦Cx出现重构,可影响心肌细胞电传导的极性,出现传导阻滞或折返,引发心律失常.实验通过快速心房起搏建立房颤模型,观察其对心房Cx40和Cx45及心房心肌纤维化的影响,并对两者相关性进行研究.方法 16只健康杂种犬随机分为模型组和对照组,2组犬均在X线下置入心房"J"型电极于右心耳,模型组予以400次/min快速起搏,而对照组维持窦性心律.连续起搏10周,分别在2、4、6、8周检测肢导联心电图.对于10周后未出现房颤的犬予以房颤诱发.实验结束后,取左心房组织制备心肌组织切片.Masson染色观察心房心肌胶原改变,电镜观察心房心肌超微结构及闰盘改变,放射免疫法测定血清中Ⅲ型前胶原氨基端肽和Ⅳ型胶原,免疫组化法检测Cx40及Cx45的表达.结果 模型组在快速起搏10周后均未出现自发性房颤,但其中有2只犬分别出现心房扑动和房性早搏,模型组和对照组予以Burst刺激后,模型组房颤诱发率可达66.7%,而对照组均正常.与对照组相比,模型组心房心肌胶原容积分数(collagen volume fraction,CVF)增加(P＜0.05),尤以心内膜和心房肌细胞间质纤维化明显.电镜下,模型组心房肌细胞超微结构可见肌纤维紊乱、断裂,胶原纤维增生,闰盘结构扭曲、扩张,部分闰盘缝隙消失.模型组血清中Ⅲ型前胶原氨基端肽和Ⅳ型胶原水平较对照组显著增高(P＜0.05);模型组心房心肌Cx40表达较对照组增加(P＜0.05),而Cx45蛋白改变二组差异无统计学意义(P＞0.05).将心房心肌组织CVF与Cx40行相关性分析,结果显示CVF与Cx40呈正相关(r=0.671).结论 犬心房快速起搏能诱导左心房组织心肌纤维化和Cx40表达增加,但对Cx45无影响,同时发现Cx40的改变程度受心房心肌纤维化程度的影响.
目的 心房顫動(房顫)的髮生及維持機製與心房結構重構和電重構有關.縫隙連接蛋白(connexin,Cx)是心肌閏盤的重要組成結構.一旦Cx齣現重構,可影響心肌細胞電傳導的極性,齣現傳導阻滯或摺返,引髮心律失常.實驗通過快速心房起搏建立房顫模型,觀察其對心房Cx40和Cx45及心房心肌纖維化的影響,併對兩者相關性進行研究.方法 16隻健康雜種犬隨機分為模型組和對照組,2組犬均在X線下置入心房"J"型電極于右心耳,模型組予以400次/min快速起搏,而對照組維持竇性心律.連續起搏10週,分彆在2、4、6、8週檢測肢導聯心電圖.對于10週後未齣現房顫的犬予以房顫誘髮.實驗結束後,取左心房組織製備心肌組織切片.Masson染色觀察心房心肌膠原改變,電鏡觀察心房心肌超微結構及閏盤改變,放射免疫法測定血清中Ⅲ型前膠原氨基耑肽和Ⅳ型膠原,免疫組化法檢測Cx40及Cx45的錶達.結果 模型組在快速起搏10週後均未齣現自髮性房顫,但其中有2隻犬分彆齣現心房撲動和房性早搏,模型組和對照組予以Burst刺激後,模型組房顫誘髮率可達66.7%,而對照組均正常.與對照組相比,模型組心房心肌膠原容積分數(collagen volume fraction,CVF)增加(P＜0.05),尤以心內膜和心房肌細胞間質纖維化明顯.電鏡下,模型組心房肌細胞超微結構可見肌纖維紊亂、斷裂,膠原纖維增生,閏盤結構扭麯、擴張,部分閏盤縫隙消失.模型組血清中Ⅲ型前膠原氨基耑肽和Ⅳ型膠原水平較對照組顯著增高(P＜0.05);模型組心房心肌Cx40錶達較對照組增加(P＜0.05),而Cx45蛋白改變二組差異無統計學意義(P＞0.05).將心房心肌組織CVF與Cx40行相關性分析,結果顯示CVF與Cx40呈正相關(r=0.671).結論 犬心房快速起搏能誘導左心房組織心肌纖維化和Cx40錶達增加,但對Cx45無影響,同時髮現Cx40的改變程度受心房心肌纖維化程度的影響.
목적 심방전동(방전)적발생급유지궤제여심방결구중구화전중구유관.봉극련접단백(connexin,Cx)시심기윤반적중요조성결구.일단Cx출현중구,가영향심기세포전전도적겁성,출현전도조체혹절반,인발심률실상.실험통과쾌속심방기박건립방전모형,관찰기대심방Cx40화Cx45급심방심기섬유화적영향,병대량자상관성진행연구.방법 16지건강잡충견수궤분위모형조화대조조,2조견균재X선하치입심방"J"형전겁우우심이,모형조여이400차/min쾌속기박,이대조조유지두성심률.련속기박10주,분별재2、4、6、8주검측지도련심전도.대우10주후미출현방전적견여이방전유발.실험결속후,취좌심방조직제비심기조직절편.Masson염색관찰심방심기효원개변,전경관찰심방심기초미결구급윤반개변,방사면역법측정혈청중Ⅲ형전효원안기단태화Ⅳ형효원,면역조화법검측Cx40급Cx45적표체.결과 모형조재쾌속기박10주후균미출현자발성방전,단기중유2지견분별출현심방복동화방성조박,모형조화대조조여이Burst자격후,모형조방전유발솔가체66.7%,이대조조균정상.여대조조상비,모형조심방심기효원용적분수(collagen volume fraction,CVF)증가(P＜0.05),우이심내막화심방기세포간질섬유화명현.전경하,모형조심방기세포초미결구가견기섬유문란、단렬,효원섬유증생,윤반결구뉴곡、확장,부분윤반봉극소실.모형조혈청중Ⅲ형전효원안기단태화Ⅳ형효원수평교대조조현저증고(P＜0.05);모형조심방심기Cx40표체교대조조증가(P＜0.05),이Cx45단백개변이조차이무통계학의의(P＞0.05).장심방심기조직CVF여Cx40행상관성분석,결과현시CVF여Cx40정정상관(r=0.671).결론 견심방쾌속기박능유도좌심방조직심기섬유화화Cx40표체증가,단대Cx45무영향,동시발현Cx40적개변정도수심방심기섬유화정도적영향.
Objective Electrical and structural remodeling are of importance for the occurrence and maintenance of atrial fibrillation. We observed association between atrial connexin protein expression and fibrosis in a canine model of prolonged rapid atrial pacing. Methods "J"-type electrodes were placed in the right atrial appendage under the guidance of X-ray in 16 dogs, Animals in model group ( n = 8) received fast pacing (400 beats/min ) for 10 weeks while animals in control group (n =8) maintained at sinus rhythm.Limb-lead ECGs were recorded at 2,4,6,8 weeks respectively. Burst stimulation was applied to induce atrial fibrillation in all animals after 10 weeks, animals were sacrificed thereafter and the left atrial tissues were taken for myocardial collagen measurement ( Masson staining) and myocardial ultrastructure examination and detection of protein expression of connexin ( Cx ) 40 and 45 ( immune staining). Procollagen type Ⅲ N-terminal peptide and type Ⅳ collagen in serum were also detected by radioimmunoassay. Results Two dogs died in model group due to atrial rupture induced cardiac tamponade or lung emboli. Spontaneously atrial fibrillation was not observed in all animals, but two dogs developed atrial flutter and atrial premature beats. Atrial fibrillation was induced by burst stimulation in 4 out of 6 dogs in model group and in none of the dogs in control group. Atrial myocardial collagen volume fraction was significantly increased in model group compared with the control group (P ＜ 0. 05). Ultrastructure examination in atrial tissue evidenced disorder,fracture,collagen fiber proliferation, mitochondrial swelling, blurred cristae, and intercalated disc distortion,expansion, part of gap junction disappears in model group. The serum levels of procollagen type Ⅲ N-terminal peptide and type Ⅳ collagen in model group were significantly higher than in the control group ( P ＜ 0. 05 ). The protein expression of Cx40 in atrial myocardium in model group was significantly higher than in control group (P ＜ 0. 05 ), while Cx45 protein expression was similar between two groups (P ＞0. 05). The left atrial CVF was positively correlated with Cx40 ( r = 0. 671, P ＜ 0. 01 ). Conclusion Increased myocardial fibrosis is positively correlated with upregulation of myocardial Cx40 protein expression in left atrium in rapid atrial paced canine.
