中国循环杂志
中國循環雜誌
중국순배잡지
CHINESE CIRCULATION JOURNAL
2014年
12期
1024-1028
,共5页
鲍宏刚%张卫泽%李涛%陈永清%马凌%贾俊杰%徐志勇
鮑宏剛%張衛澤%李濤%陳永清%馬凌%賈俊傑%徐誌勇
포굉강%장위택%리도%진영청%마릉%가준걸%서지용
丙氨酰谷氨酰胺%心肌纤维化%缝隙连接蛋白43%细胞外信号调节激酶%热休克蛋白70
丙氨酰穀氨酰胺%心肌纖維化%縫隙連接蛋白43%細胞外信號調節激酶%熱休剋蛋白70
병안선곡안선알%심기섬유화%봉극련접단백43%세포외신호조절격매%열휴극단백70
Ala-Gln%Myocardial ifbrosis%Connexin43%Extracellular signal-regulated kinase%Heat shock protein 70
目的：研究丙氨酰谷氨酰胺（Ala-Gln）诱导热休克蛋白70（HSP70）高表达对心肌缺血模型大鼠心肌纤维化及缝隙连接蛋白43（Cx43）重构的影响及其机制。<br> 方法：32只SPF级雄性SD大鼠（200±20）g，按随机数字表法随机等分为4组：对照组、盐酸异丙肾上腺素（ISO）[5mg/（kg·d）]组（模型组）、ISO[5mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]组（干预组）、ISO[5mg/（kg·d）]+槲皮素[100mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]+二甲基亚矾（DMSO）组（槲皮素组）。每组每天1次给予相应试剂，ISO连续给药7d后停止，余处理继续至第4周时处死大鼠。伊红素（HE）、Masson染色法观察心肌纤维化情况并计算胶原容积分数；免疫组织化学法观察心肌组织中HSP70、磷酸化细胞外信号调节激酶1/2（p-ERK1/2）及Cx43分布，并通过软件进行半定量分析。<br> 结果：伊红素、Masson染色结果显示对照组无明显心肌纤维化，模型组和槲皮素组出现明显的纤维化，而干预组较模型组和槲皮素组心肌纤维化程度均减弱（P均<0.01），干预组与对照组的心肌纤维化程度无明显差异（P>0.05）。对照组、模型组、槲皮素组中HSP70的含量差异无统计学意义（P>0.05），而干预组中HSP70的含量较上述各组明显升高,且差异有统计学意义（P均<0.01）。心肌组织中p-ERK1/2的含量干预组较模型组、槲皮素组均降低，差异有统计学意义（P均<0.01）。Cx43含量在对照组与干预组中差异无统计学意义且呈线性规律分布，干预组较模型组和槲皮素组均增加，差异有统计学意义（P均<0.01），分布无规律性，且侧面分布相对增多。<br> 结论：Ala-Gln诱导HSP70高表达可减轻ISO诱发的心肌缺血模型大鼠心肌纤维化程度和Cx43的重构，其机制可能与HSP70下调p-ERK1/2的表达，抑制细胞外信号调节激酶通路激活有关。
目的：研究丙氨酰穀氨酰胺（Ala-Gln）誘導熱休剋蛋白70（HSP70）高錶達對心肌缺血模型大鼠心肌纖維化及縫隙連接蛋白43（Cx43）重構的影響及其機製。<br> 方法：32隻SPF級雄性SD大鼠（200±20）g，按隨機數字錶法隨機等分為4組：對照組、鹽痠異丙腎上腺素（ISO）[5mg/（kg·d）]組（模型組）、ISO[5mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]組（榦預組）、ISO[5mg/（kg·d）]+槲皮素[100mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]+二甲基亞礬（DMSO）組（槲皮素組）。每組每天1次給予相應試劑，ISO連續給藥7d後停止，餘處理繼續至第4週時處死大鼠。伊紅素（HE）、Masson染色法觀察心肌纖維化情況併計算膠原容積分數；免疫組織化學法觀察心肌組織中HSP70、燐痠化細胞外信號調節激酶1/2（p-ERK1/2）及Cx43分佈，併通過軟件進行半定量分析。<br> 結果：伊紅素、Masson染色結果顯示對照組無明顯心肌纖維化，模型組和槲皮素組齣現明顯的纖維化，而榦預組較模型組和槲皮素組心肌纖維化程度均減弱（P均<0.01），榦預組與對照組的心肌纖維化程度無明顯差異（P>0.05）。對照組、模型組、槲皮素組中HSP70的含量差異無統計學意義（P>0.05），而榦預組中HSP70的含量較上述各組明顯升高,且差異有統計學意義（P均<0.01）。心肌組織中p-ERK1/2的含量榦預組較模型組、槲皮素組均降低，差異有統計學意義（P均<0.01）。Cx43含量在對照組與榦預組中差異無統計學意義且呈線性規律分佈，榦預組較模型組和槲皮素組均增加，差異有統計學意義（P均<0.01），分佈無規律性，且側麵分佈相對增多。<br> 結論：Ala-Gln誘導HSP70高錶達可減輕ISO誘髮的心肌缺血模型大鼠心肌纖維化程度和Cx43的重構，其機製可能與HSP70下調p-ERK1/2的錶達，抑製細胞外信號調節激酶通路激活有關。
목적：연구병안선곡안선알（Ala-Gln）유도열휴극단백70（HSP70）고표체대심기결혈모형대서심기섬유화급봉극련접단백43（Cx43）중구적영향급기궤제。<br> 방법：32지SPF급웅성SD대서（200±20）g，안수궤수자표법수궤등분위4조：대조조、염산이병신상선소（ISO）[5mg/（kg·d）]조（모형조）、ISO[5mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]조（간예조）、ISO[5mg/（kg·d）]+곡피소[100mg/（kg·d）]+Ala-Gln [0.75mg/（kg·d）]+이갑기아반（DMSO）조（곡피소조）。매조매천1차급여상응시제，ISO련속급약7d후정지，여처리계속지제4주시처사대서。이홍소（HE）、Masson염색법관찰심기섬유화정황병계산효원용적분수；면역조직화학법관찰심기조직중HSP70、린산화세포외신호조절격매1/2（p-ERK1/2）급Cx43분포，병통과연건진행반정량분석。<br> 결과：이홍소、Masson염색결과현시대조조무명현심기섬유화，모형조화곡피소조출현명현적섬유화，이간예조교모형조화곡피소조심기섬유화정도균감약（P균<0.01），간예조여대조조적심기섬유화정도무명현차이（P>0.05）。대조조、모형조、곡피소조중HSP70적함량차이무통계학의의（P>0.05），이간예조중HSP70적함량교상술각조명현승고,차차이유통계학의의（P균<0.01）。심기조직중p-ERK1/2적함량간예조교모형조、곡피소조균강저，차이유통계학의의（P균<0.01）。Cx43함량재대조조여간예조중차이무통계학의의차정선성규률분포，간예조교모형조화곡피소조균증가，차이유통계학의의（P균<0.01），분포무규률성，차측면분포상대증다。<br> 결론：Ala-Gln유도HSP70고표체가감경ISO유발적심기결혈모형대서심기섬유화정도화Cx43적중구，기궤제가능여HSP70하조p-ERK1/2적표체，억제세포외신호조절격매통로격활유관。
Objective: To investigate the effects of Ala-Gln induced heat shock protein 70 (HSP70) expression on myocardial ifbrosis and connexin43 (Cx43) remodeling in experimental rats’ model. <br> Methods: A total of 32 SPF male SD rats were randomly divided into 4 groups:①Control group,②Model group, the rats received isoprenaline (ISO) 5m/(kg·d),③Intervention group, the rats received ISO+Ala-Gln 0.75mg/(kg·d),④Quercetin group, the rats received ISO+quercetin 100mg/(kg·d)+Ala-Gln+DMSO. n=8 in each group. All animals were treated for 7 days and killed in 4 weeks for relevant examinations. HE and Masson staining was conducted to observe myocardial ifbrosis, then calculate collagen volume fraction; immunohistochemistry was applied to measure myocardial HSP70 expression, <br> extracellular signal regulated kinase (p-ERK1/2) and Cx43 distribution, then conduct semi-quantitative analysis by speciifc soft ware. <br> Results: HE and Masson staining indicated that Control group had no obvious myocardial ifbrosis, Model group and Quercetin group had obvious ifbrosis, and Intervention group showed less ifbrosis than the other 2 groups, all P<0.01. The fibrosis level was similar between Intervention group and Control group, P>0.05. The myocardial HSP70 expression was similar among Control, Model and Quercetin groups, P>0.05, while HSP70 expression was signiifcantly higher in Intervention group than the other 3 groups, all P<0.01. The myocardial p-ERK1/2 level was lower in Intervention group than Model and Quercetin groups, all P<0.01. The myocardial Cx43 level was similar between Control group and Intervention group with linear distribution, while it was higher in Intervention group than Model and Quercetin groups with disordered distribution, all P<0.01. <br> Conclusion: Ala-Gln inducing the higher expression of HSP70, which may reduce myocardial ifbrosis in experimental rats, it could be because of HSP70 down regulating p-ERK1/2 expression and inhibiting ERK signaling pathway.
