| Objective:This study aimed at establishing a rat model of Rac1b knockout and investigated the effect of Rac1b deficiency on atrial fibrosis induced by AngⅡ,providing new ideas for the clinical treatment of atrial fibrillation.Methods:The study was divided into vitro and vivotwo part.一.Vitro partBy isolating and culturing primary atrial fibroblasts of Rac1b+/+and Rac1b-/-genotype Sprague-Dawley,Then treatment of atrial fibroblasts with angiotensin Ⅱ.The effect of angiotensin Ⅱ on cardiac fibroblasts apoptosis and lack of Rac1b gene expression on cardiac fibroblasts apoptosis was detected by flow cytometry.二.Vivo partAn osmoticmini-pump was implanted for subcutaneous infusion of angiotensin Ⅱ on eight-week-old Rac1b-/-male rat and Rac1b+/+littermates,and set up the corresponding control group,angiotensin Ⅱ-induced atrial fibrosis model was constructed.Rac1b mRNA expression were measured by semi-quantitative RT-PCR,To evaluate the expression levels of Rac1b、type ⅡI collagen and TGF-β1 were detected by western blot analysis,Masson’s trichrome staining was used to evaluate the degree of atrial fibrosis.The size of the left atrium were evaluated by echocardiography.Results:angiotensin Ⅱ induces cardiomyocyte fibroblast apoptosis,Moreover,the rate of apoptosis of cardiac fibroblasts with lack of Rac1b gene increased.It is highly suggested that Rac1b may antagonist cardiac fibroblasts apoptosis and further promote the development of atrial fibrosis.Angiotensin Ⅱ induced the up-regulation of fibrosis-related factors expression and increased the degree of atrial fibrosis.Compared with Rac1b+/+littermates,Rac1b-/-rat’s fibrosis-related genes and proteins expression were down-regulated,the degree of atrial fibrosis w3ere lighter.It is suggested that the Rac1b gene may participate in the molecular mechanism of angiotensin Ⅱ-mediated atrial fibrosis.Conclusion:Rac1b may be involved in AngⅡ-induced atrial fibrosis as a downstream effector of AngⅡ. |
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