| Background and ObjectiveVentricular remodeling as subsequent changes of acute myocardial infarction, thinning of the ventricular walls of the myocardial infarction area, and thickening of the ventricular walls of non-infarcted zone, resulted in left ventricular systolic and diastolic dysfunction, left ventricular dilation. Shortage of energy supply and use of obstacles in myocardial cells lead to myocardial cell necrosis, fibrosis, is one of the important factors of ventricular remodeling, which is an important index on prognosis of acute myocardial infarction. Neurohumoral regulation mechanism activated after myocardial infarction,, especially the activation of renin-angiotensin aldosterone system (RAAS), accelerating the ventricular remodeling process, Ang-Ⅱ can stimulate secretion of fibroblasts and to produce transforming growth factor (TGF-beta1), TGF-beta1induce myocardial fibrosis through stimulation of extracellular matrix protein expression.Periostin is one kind of extracellular matrix proteins, involved in cell adhesion. Human Periostin gene located on chromosome13, is a terminal glycosylation protein connection by disulfide compounds with heparin combined. Numerous studies have found that, Periostin has a closely connection with Coronary heart disease, Periostin can Involved in the formation of the physiologic and pathologic fibrosis, resulted in ventricular remodeling by directly interacting with other ECM proteins such as collagen Ⅰ, collagen Ⅴ, and fibronectin.In recent years, the cardiovascular protective effect of statins against myocardial fibrosis, platelet aggregation and thrombosis and stable plaques independent of regulating blood-lipid are closely watched. Clinical evidence had been demonstrate that statins can improve ventricular remodeling. Our experiment established model of acute myocardial infarction (MI) in rats by ligating the left anterior descending, to observe the expression of Periostin in myocardial infarction, intervention effect of rosuvastatin, and to investigate the improvement of myocardial reconstruction mechanism. In order to provide a new experimental basis by using rosuvastatin to improve myocardial remodeling after acute myocardial infarction (MI).Methods8weeks SD female rats, weight250g～300g, provided by experimental animal center of zhengzhou university. establish models of acute myocardial infarction (AMI) by ligating LAD. Another15rats were tested with pierced but not ligated LAD (n=15) as Sham-operated group (Sham). Give400000units/kg/day penicillin to prevent infection after operation, a total of3days. twenty four hours later, the models were randomly divided into acute myocardial infarction (AMI) as control group (n=15) and rosuvastatin intervention (ROS) group (n=15); Rats in ROS group were given rosuvastatin by gavage at10mg/(kg-d) dose levels to soluble in2mL clear water, whereas rats in the other two groups were given2mL clear water each day. All experimental rats were free diet.4weeks later, put all rats to death by cervical dislocation, extract the heart, along the left ventricular long axis in infarction devide in two, take the infarct border zone, paraffin embedding sectioning after10%formaldehyde fixed, observe cardiac morphological changes by HE dyeing, observe the myocardial fibrosis by MASSON staining, and calculate myocardial collagen volume fraction; to observe the expression changes of Ang-Ⅱ and Periostin through immunohistochemical method; Liquid nitrogen preservation of another part, to detect the expression changes of TGF-beta1and Periostin by RT-PCR.Results 1. Survival situation of rats after4weeks later:In Sham group twelve rats survived while eleven did in ROS group and ten in AMI group.2. Overview of heart sample:Compared with ROS group, infarct area of ventricular wall collapse, pale color, thinner of ventricular wall in AMI group, while no significant changes occured in Sham group.3. HE staining showed that vacuoles change in myocardial cells, disordered arrangement of the nuclei, myocardial fiber rupture in AMI group, compared with AMI group, less vacuoles change in myocardial cells, myocardial arranged relatively orderer, less rupture of myocardial fiber in ROS group.4. Masson staining showed that a large number of collagen fibers formed in AMI group, very small amounts of collagen fibers formed in Sham group, the changes of ROS group in between. Myocardial CVF reduced in ROS group compared with rats in AMI group (P<0.05), both ROS group and AMI group were significantly higher than those in Sham group (P<0.05).5. Immunohistochemical staining showed that Overexpression of Periostin in myocardial cell cytoplasm in AMI group, relatively reduced in ROS group; Expression of Ang-Ⅱ and Periostin protein were reduced in ROS group compared with rats in AMI group (P<0.05), both ROS group and AMI group were significantly higher than those in the Sham group (P<0.05).6. RT-PCR showed that TGF-β1mRNA and Periostin mRNA were reduced in the ROS group compared with rats in the AMI group (P<0.05), both ROS group and AMI group were significantly higher than those in the Sham group (P<0.05).Conclusions1. Expression of Periostin in acute myocardial infarction group significantly increased compared with Sham group, and the collagen formation were significantly increased than that in Sham group, suggestted that Periostin may involved in the occurrence of ventricular remodeling after myocardial infarction.2. Ang Ⅱ and TGF beta1as Periostin’s upstream factors increased in the infarct myocardial border zone, may involved in the occurrence of ventricular remodeling after myocardial infarction.3. Expression of Periostin in ROS group significantly lower than that in myocardial infarction group, AngⅡ and TGF beta-1as it’s upstream factors were significantly lower than that in myocardial infarction group, suggestted that ROS improved ventricular remodeling may be related to inhibition of AngⅡ-TGF beta-1-Periostin signaling pathways. |
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