發(fā)布時間：2018-03-28 13:54

  本文選題：心肌病　切入點：擴張型　出處：《重慶醫(yī)學》2017年11期

【摘要】：目的研究高遷移率族蛋白1(HMGB1)及其炎癥信號通路[HMGB1-Toll樣受體4(TLR4)/晚期糖基化終產(chǎn)物受體(RAGE)-核因子κB(NF-κB)-細胞因子]在大鼠擴張型心肌病(DCM)中的表達,并探討其在DCM發(fā)生、發(fā)展中的意義。方法以SD大鼠構建DCM模型,雄性大鼠42只,分為對照組(20只)和DCM組(22只)。以腹腔注射阿霉素進行造模,DCM組腹腔注射阿霉素1.0mg/kg(生理鹽水稀釋至1mg/mL),對照組腹腔注射等量生理鹽水,1周2次,用藥6周,停藥觀察2周。造模后隨機抽取2只大鼠行心臟彩超及病理檢查證實造模是否成功,余大鼠行心臟彩超檢查;留取血標本,進行血清白細胞介素(IL)-1、IL-6、腫瘤壞死因子-α(TNF-α)、腦利鈉肽(BNP)、C反應蛋白(CRP)水平的測定;處死大鼠留取左心室心肌組織標本,進行心肌組織HMGB1、TLR4、RAGE、NF-κB的mRNA表達測定;進行心肌組織病理及電鏡檢查。結果 8周后對照組無死亡,DCM組死亡4只,其余18只隨機抽取2只大鼠證實造模成功。DCM組左心室舒張末期內(nèi)徑(LVEDD)、左心室收縮末期內(nèi)徑(LVESD)較對照組明顯升高(P0.05);左心室射血分數(shù)(LVEF)、左心室短軸收縮率(FS)較對照組明顯下降(P0.05)。DCM組心肌組織HMGB1、TLR4、RAGE、NF-κB mRNA的表達較對照組明顯升高(P0.05);HMGB1mRNA與TLR4mRNA、RAGE mRNA及NF-κB mRNA呈正相關(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水平較對照組明顯升高(P0.05);HMGB1mRNA的表達分別與IL-1、IL-6、TNF-α、CRP水平呈正相關(r=0.944,P=0.002;r=0.988,P=0.000;r=0.968,P=0.000;r=0.961,P=0.000)。結論 HMGB1及其炎癥信號通路(HMGB1-TLR4/RAGE-NF-κB-細胞因子)在大鼠DCM中呈現(xiàn)高表達,并與心腔大小及心功能相關,提示其可能是DCM發(fā)生、發(fā)展的病理生理機制之一。
[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- 偽, BNPP-C-reactive protein (CRP) in serum IL-6, TNF- 偽 -TNF- 偽 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- 偽 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- 偽 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- 偽 mRNA and the level of IL-1IL-6TNF- 偽 mRNA. Conclusion the expression of HMGB1 mRNA is positively correlated with the level of IL-1IL-6TNF- 偽 mRNA and the level of IL-1IL-6TNF- 偽 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.
【作者單位】： 南京中醫(yī)藥大學無錫附屬醫(yī)院;江蘇省血吸蟲病防治研究所/衛(wèi)生部重點實驗室;
【基金】：無錫市醫(yī)管中心科研面上項目(YGZXM14047)
【分類號】：R542.2

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