| Purpose:In this study,we investigated the effect of RXRa agonist Bexarotene(Bex)on the TGF-β1 / Smads signaling pathway in myocardial tissue of rats with myocardial infarction and its effect on cardiac structure and function.Methods:The acute myocardial infarction model of SD rats was made by ligating the left anterior descending coronary artery.40 male SD rats were randomly divided into 5 groups: 1)Group A: control group(control,n = 8);2)Group B: sham operation group(Sham,n = 8);3)Group C: myocardial infarction group(MI,n = 8);4)Group D: myocardial infarction Bex10mg/ kg/d treatment group(MI + Bex10,n = 8);5)Group E: myocardial infarction Bex30mg/kg/d treatment group(MI + Bex30,n = 8).After 4 weeks,weigh the body weight,and the cardiac structure and function were examined by ultrasonography.Animals are sacrificed after anesthesia and taken as needed.HE and Sirius red staining were used to observe the changes of myocardial tissue,collagen distribution and content in rats,and the levels of TGF-β1、Col-Ⅰ、Col-III in myocardium,plasma BNP and serum IL-10 、TNF-α were detected by ELISA.The level of CK-MB was measured by immunosuppressive method.The levels of LDL,CR,ALT and AST were measured by enzyme colorimetry.The levels of HDL-C and LDL-C were measured by homogeneous enzyme colorimetric method.The levels of TCHO,TG and NEFA were measured by oxidase method.The level of BUN was measured by urea synthase method.The levels of TGF-β1,Smad2,P-Smad2,Smad3,P-Smad3 and Smad7 were measured by Western blotting.The apoptosis of myocardium was detected by Tunel method.The changes of myocardial tissue were observed by electron microscopy.Results:1)Compared with the control group and the Sham group,the left anterior wall of the MI group was thinner and the myocardial cells were reduced and arranged disorderly.A large number of fibrous tissue deposits were found in the infarct area and the infarct margin;Compared with MI group,the left ventricular anterior wall of MI + Bex10 group and MI + Bex30 group was thicker,the number of cardiomyocytes was more and more arranged,and the fibrous tissue deposited in the infarcted and infarcted areas was less;Compared with MI + Bex10 group,the left ventricular anterior wall and the number of cardiomyocytes in the MI + Bex30 group were more neat,and the fibrous tissue hyperplasia in the infarcted and infarcted areas was less.2)Compared with Control group and Sham group,LVPWd and LVPWs were significantly increased in MI group(LVPWd MI 1.74 ± 0.14 mm vs Control 1.58 ± 0.10 mm,P <0.05;LVPWs MI 2.55 ± 0.11 mm vs Sham 2.36 ± 0.11 mm,P <0.05),EF was significantly decreased(EF MI 38.58 ± 5.17% vs Sham 72.40 ± 1.37%,P <0.05);Compared with MI group,LVPWd and LVPWs were significantly decreased in MI + Bex10 group and MI + Bex30 group(LVPWd MI 1.74 ± 0.14 mm vs MI + Bex10 1.58 ± 0.07 mm,P <0.05;LVPWs MI 2.55±0.11 mm vs MI+Bex10 2.18±0.28 mm,P<0.05;LVPWs MI 2.55±0.11 mm vs MI+Bex30 2.19±0.22 mm,P<0.05),EF was significantly increased(EF MI 38.58±5.17% vs MI+Bex10 47.36±7.34%,P<0.05;EF MI 38.58±5.17% vs MI+Bex30 49.26±6.57%,P<0.05);Compared with MI + Bex10 group,LVEDd was significantly increased in MI + Bex30 group(MI + Bex10 8.04 ± 1.05 mm vs MI + Bex30 8.79 ± 0.75 mm,P <0.05),but there was no significant difference between LVEDs,LVPWd and LVPWs.3)Compared with Control group and Sham group,the levels of Collagen-Ⅰ and Collagen-III in MI group were significantly increased(P <0.05);Compared with MI group,Collagen-Ⅰ and Collagen-III levels were decreased in MI + Bex10 group and MI + Bex30 group(P <0.05);Compared with MI + Bex10 group,the levels of Collagen-Ⅰ and Collagen-III in MI + Bex30 group were significantly decreased(P <0.05).4)Compared with control group and Sham group,the levels of TGF-β1,P-Smad2,P-Smad3 and Smad7 in the left ventricular anterior wall of MI group were significantly increased(P <0.05);Compared with MI group,the levels of TGF-β1 and P-Smad3 in MI + Bex10 group and MI + Bex30 group were significantly decreased(P <0.05),while the levels of P-Smad2 and Smad7 were significantly increased(P <0.05);The levels of TGF-β1 and P-Smad3 in MI + Bex30 group were significantly lower than those in MI + Bex10 group(P <0.05),while The levels of P-Smad2 and Smad7 in MI + Bex30 group were significantly increased than those in MI + Bex10 group(P <0.05).There was no significant difference in Smad2 and Smad3 levels between MI + Bex30 group and MI + Bex10 group.5)Compared with Control group and Sham group,The apoptotic index of MI group was significantly increased in infarct area,infarcted margin area and non-infarcted area(P <0.05);Compared with MI group,the apoptotic index of MI + Bex10 and MI + Bex30 group was significantly lower than that of infarct area,infarcted margin area and non-infarcted area(P <0.05);Compared with MI + Bex10 group,the apoptotic index of MI + Bex30 was significantly lower in infarcted margin area(P <0.05).There was no significant difference in apoptotic index between MI + Bex10 and MI + Bex30 groups in infarcted and non-infarcted areas.6)Compared with the control group and Sham group,MI group of myocardial fibers arranged sparse and disorder,part of the cardiomyocyte plasma membrane incomplete mitochondria leakage and swelling state,showing increased autophagylase;accompanied by focal cell necrosis and atrophy,interstitial mass of collagen fibers can be seen;Compared with MI group,MI + Bex10 group and MI + Bex30 group,most of the muscle fibers arranged closely,the myocardium plasma membrane is relatively complete,no mitochondria leakage,showing a small amount of autophagy lysosomes,interstitial collagen hyperplasia is not obvious;Compared with MI + Bex10 group,MI + Bex30 group of muscle fibers arranged more closely,the myocardium plasma membrane is more complete,and interstitial collagen hyperplasia less.Conclusion: The RXRα receptor agonist Bex improves the ventricular structure and function after myocardial infarction by regulating the TGF-β1 / Smads signaling pathway. |
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