摘要
目的探讨过氧化物酶体增殖物激活型受体γ(peroxisome proliferator activated receptorγ,PPARγ)不同表达与大鼠心肌间质纤维化之间关系以及其在心肌间质纤维化进程中的作用和机制。方法雄性SD大鼠48只随机分成4组:(1)对照组(C组)16只,采用0.05%ISO[5mg/(kg·d)×10d]皮下注射制作大鼠心肌纤维化模型;(2)早期干预组(Pa组)12只,造模同时给予PPARγ激动剂罗格列酮100mg/(kg·d),腹腔注射56d;(3)晚期干预组(Pp组)12只,造模10d后同样应用罗格列酮46d;(4)空白组(B组)8只。建模后观测各组左心室质量指数、心肌PPARγ mRNA水平、左室心肌组织羟脯氨酸浓度、胶原容积积分(collagen volume fraction,CVF)并检测PPARγ、TGF-β、CTGF、MMP9表达。结果在观测指标左心室质量指数、CVF、心肌组织羟脯氨酸浓度和PPARγ、TGF-β、CTGF、MMP9表达上,Pa组、Pp组和C组均较B组明显增加(P<0.05),Pa组和Pp组均较C组明显减少(P<0.05),Pa组减少更明显。结论 PPARγ可能在心肌间质纤维化进程中发挥重要作用,可能是促进心肌胶原合成的重要信号分子。PPARγ活化可减少TGF-β、CTGF、MMP9表达和胶原沉积,从而减缓ISO诱导的心肌纤维化,早期干预效果更明显,此作用机制可能通过抑制TGF-β、CTGF的过度表达来实现。
Objective To study the role of peroxisome proliferator activated receptor γ （PPARγ） in myocardial interstitial fibrosis. Methods Forty eight male SD rats were randomly divided into 4 groups：（1） the control group （Group C,n=16）,received 0.05% ISO [5 mg/（kg·d）×10 d] subcutaneous injection to creat myocardial fibrosis model; （2） the early intervention group （Group Pa,n=12）,received PPARγ agonist rosiglitazone [100 mg/（kg·d）] intraperitoneal injection combined with 0.05% ISO [5 mg/（kg·d）×10 d] subcutaneous injection; （3） the late intervention group （Group Pp,n=12）,received PPARγ agonist rosiglitazone [100 mg/（kg·d）] intraperitoneal injection 10 days after modeled with ISO; （4） blank group （Group B,n=12）. After 56 days,animals were assessed for of left ventricular mass index,collagen volume fraction （CVF）,myocardial hydroproline concentration and the expressions of myocardial PPARγ mRNA,PPARγ,TGF-β,CTGF and MMP9. Results The left ventricular mass index,CVF,myocardial hydroxyproline concentration and PPARγ,TGF-β,CTGF,MMP9 expression in group B were significantly higher than all those in Group Pa,Group Pp and Group C （P〈0.05）,and were significantly higher in Group C compared with those in Group Pa and Group Pp （P〈0.05）,with more obvious change in Group Pa. Conclusion The peroxisome proliferator-activated receptor γ plays an important role in myocardial interstitial fibrosis by promoting synthesis of myocardial collagen signaling molecules. PPARγ activation delays the ISO-induced myocardial fibrosis by inhbiting TGF-β,CTGF and MMP9 expressions,and collagen deposition. Furthermore,the effect of early intervention is much better,with the probable mechanism of inhibiting TGF-β and CTGF over expressions.
出处
《广东医学》
CAS
CSCD
北大核心
2010年第9期1084-1087,共4页
Guangdong Medical Journal
基金
国家自然科学基金(编号:30700822)
