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目的探讨Toll样受体4(TLR4)-NF-κB炎症信号通路在大鼠扩张型心肌病(DCM)中的作用。方法 42只雄性SD大鼠随机分为两组:DCM组22只,腹腔注射阿霉素1.0mg/kg,每周2次,连续6周,构建DCM模型;对照组20只,腹腔注射生理盐水1.0mg/kg。8周后行心脏彩超及心肌代谢显像检查,采用ELISA法检测血清IL-1、IL-6、TNF-α、脑钠肽(BNP)和C反应蛋白(CRP)水平,采用RT-PCR及Western blot法测定心肌组织TLR4、NF-κB mRNA及蛋白表达,分析TLR4表达与NF-κB、IL-1、IL-6、TNF-α、CRP、BNP、左心室舒张末期内径(LVEDD)及左心室射血分数(LVEF)的相关性。结果8周后检测心脏超声,DCM组大鼠LVEDD长于对照组(P<0.05),LVEF和左心室短轴收缩率低于对照组(P<0.05)。对照组大鼠心肌完整,葡萄糖代谢正常,心肌摄取~(18)氟-氟代脱氧葡萄糖(~(18) F-FDG)均匀。DCM组心肌糖代谢异常,部分心肌摄取~(18) F-FDG降低。DCM组心肌组织TLR4、NF-κB mRNA和蛋白表达较对照组升高(P<0.05)。DCM组血清IL-1、IL-6、TNF-α、CRP和BNP水平较对照组升高(P<0.05)。DCM组心肌组织TLR4与NF-κB mRNA表达呈正相关(r=0.952,P<0.01),TLR4 mRNA表达与血清IL-1、IL-6、TNF-α和CRP水平呈正相关(r=0.776、0.879、0.917和0.779,P<0.01),与BNP、LVEDD亦呈正相关(r=0.879、0.819,P<0.01),与LVEF呈负相关(r=-0.857,P<0.01)。结论TLR4-NF-κB炎症信号通路参与DCM的病理生理进程,介导心肌细胞损伤,最终导致心腔扩大,心功能减退。
Objective To investigate the role of Toll-like receptor 4 (TLR4) -FN-κB signaling pathway in dilated cardiomyopathy (DCM) in rats. Methods Forty-two male SD rats were randomly divided into two groups: DCM group (n = 22), intraperitoneal injection of doxorubicin (1.0 mg / kg) twice a week for 6 weeks, 1.0 mg / kg. The levels of serum IL-1, IL-6, TNF-α, BNP and CRP were measured by ELISA. The expression of C-reactive protein (CRP) The expressions of TLR4 and NF-κB mRNA and protein were detected by immunohistochemistry. The expressions of TLR4 and NF-κB, IL-1, IL-6, TNF-α, CRP, BNP, left ventricular end-diastolic dimension (LVEDD) Correlation of Blood Score (LVEF). Results Echocardiography was performed after 8 weeks. LVEDD in DCM group was longer than that in control group (P <0.05), and LVEF and left ventricular short axis were lower than those in control group (P <0.05). The control group had intact myocardium, normal glucose metabolism, and ~ (18) Fluoro-fluorodeoxyglucose (~ (18) F-FDG). DCM group myocardial glucose metabolism, some myocardial uptake of ~ (18) F-FDG decreased. The expression of TLR4 and NF-κB mRNA and protein in DCM group were higher than those in control group (P <0.05). The levels of IL-1, IL-6, TNF-α, CRP and BNP in DCM group were higher than those in control group (P <0.05). The levels of TLR4 and NF-κB mRNA in myocardium of DCM group were positively correlated (r = 0.952, P <0.01). The expression of TLR4 mRNA was positively correlated with the level of IL-1, IL-6, TNF- , 0.917 and 0.779, respectively, P <0.01). There was also a positive correlation with BNP and LVEDD (r = 0.879, 0.819, P <0.01) and negative correlation with LVEF (r = -0.857, P <0.01). Conclusion The TLR4-NF-κB inflammatory signaling pathway is involved in the pathophysiology of DCM and mediates the injury of cardiomyocytes, leading to the enlargement of cardiac chambers and cardiac dysfunction.