高迁移率族蛋白1及其炎症信号通路在大鼠扩张型心肌病中的表达及意义

发布时间：2018-03-28 13:54

本文选题：心肌病　切入点：扩张型　出处：《重庆医学》2017年11期

【摘要】：目的研究高迁移率族蛋白1(HMGB1)及其炎症信号通路[HMGB1-Toll样受体4(TLR4)/晚期糖基化终产物受体(RAGE)-核因子κB(NF-κB)-细胞因子]在大鼠扩张型心肌病(DCM)中的表达,并探讨其在DCM发生、发展中的意义。方法以SD大鼠构建DCM模型,雄性大鼠42只,分为对照组(20只)和DCM组(22只)。以腹腔注射阿霉素进行造模,DCM组腹腔注射阿霉素1.0mg/kg(生理盐水稀释至1mg/mL),对照组腹腔注射等量生理盐水,1周2次,用药6周,停药观察2周。造模后随机抽取2只大鼠行心脏彩超及病理检查证实造模是否成功,余大鼠行心脏彩超检查;留取血标本,进行血清白细胞介素(IL)-1、IL-6、肿瘤坏死因子-α(TNF-α)、脑利钠肽(BNP)、C反应蛋白(CRP)水平的测定;处死大鼠留取左心室心肌组织标本,进行心肌组织HMGB1、TLR4、RAGE、NF-κB的mRNA表达测定;进行心肌组织病理及电镜检查。结果 8周后对照组无死亡,DCM组死亡4只,其余18只随机抽取2只大鼠证实造模成功。DCM组左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)较对照组明显升高(P0.05);左心室射血分数(LVEF)、左心室短轴收缩率(FS)较对照组明显下降(P0.05)。DCM组心肌组织HMGB1、TLR4、RAGE、NF-κB mRNA的表达较对照组明显升高(P0.05);HMGB1mRNA与TLR4mRNA、RAGE mRNA及NF-κB mRNA呈正相关(r=0.873,P=0.005;r=0.949,P=0.000;r=0.898,P=0.002)。血清IL-1、IL-6、TNF-α、CRP、BNP水平较对照组明显升高(P0.05);HMGB1mRNA的表达分别与IL-1、IL-6、TNF-α、CRP水平呈正相关(r=0.944,P=0.002;r=0.988,P=0.000;r=0.968,P=0.000;r=0.961,P=0.000)。结论 HMGB1及其炎症信号通路(HMGB1-TLR4/RAGE-NF-κB-细胞因子)在大鼠DCM中呈现高表达,并与心腔大小及心功能相关,提示其可能是DCM发生、发展的病理生理机制之一。
[Abstract]:Objective to investigate the expression of high mobility group protein (HMGB1) and its inflammatory signaling pathway [RAGEM-NF- 魏 NF- 魏 BM-cytokine] in rat dilated cardiomyopathy (DCM) and its role in the pathogenesis of DCM. Methods DCM model was established in SD rats with 42 male rats. The rats were divided into control group (n = 20) and DCM group (n = 22). Doxorubicin was injected intraperitoneally with adriamycin 1.0 mg / kg (diluted to 1 mg / mL of saline) in DCM group, while in control group, the same amount of saline was injected twice a week for 6 weeks. Two weeks after the drug was stopped, 2 rats were randomly selected for cardiac ultrasound and pathological examination to confirm the success of the model. The remaining rats were examined by color Doppler echocardiography, and blood samples were taken. The levels of IL-6, TNF- 伪, BNPP-C-reactive protein (CRP) in serum IL-6, TNF- 伪 -TNF- 伪 and BNP-C-reactive protein (CRP) were measured, and the mRNA expression of HMGB1TLR4 / RAGENF- 魏 B in left ventricular myocardium was determined. Results there were 4 dead rats in DCM group after 8 weeks. The remaining 18 randomly selected rats were selected to confirm the success of the model. The left ventricular end-diastolic diameter (LVEDDN) and left ventricular end-systolic diameter (LVESD) in the DCM group were significantly higher than those in the control group (P 0.05), and the left ventricular ejection fraction (LVEF) and the left ventricular short-axis contraction rate (LVEFS) were significantly higher than those in the control group. Compared with the control group, the expression of HMGB1TLR4RAGENF- 魏 B mRNA in myocardial tissue was significantly increased in the P0.05mRNA.DCM group. The expression of HMGB1 mRNA was significantly higher than that of the control group. The expression of HMGB1 mRNA was positively correlated with the levels of IL-1IL-6mRNARAGE mRNA and NF- 魏 B mRNA, respectively. There was a positive correlation between the expression of HMGB1 mRNA and the levels of r0.873P0.005P0.005P0. 0000P0. 898t. The level of serum IL-1TNF6TNF- 伪 CRPBNP was significantly higher than that of the control group. Conclusion the expression of HMGB1 mRNA is positively correlated with the level of IL-1IL-6TNF- 伪 mRNA and 40.00P2r980.8P0.000r0.000P0.000 and 0.000P0.000. Conclusion: the expression of HMGB1 mRNA is significantly higher than that of the control group (P < 0.05). The expression of HMGB1 mRNA is positively correlated with the level of IL-1IL-6TNF- 伪 mRNA and the level of IL-1IL-6TNF- 伪 mRNA. Conclusion the expression of HMGB1 mRNA is positively correlated with the level of IL-1IL-6TNF- 伪 mRNA and the level of IL-1IL-6TNF- 伪 mRNA, respectively. HMGB1-TLR4 / RAGE-NF- 魏 B- cytokines are highly expressed in rat DCM. It may be one of the pathophysiological mechanisms of the occurrence and development of DCM.
【作者单位】：南京中医药大学无锡附属医院;江苏省血吸虫病防治研究所/卫生部重点实验室;
【基金】：无锡市医管中心科研面上项目(YGZXM14047)
【分类号】：R542.2

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