目的 基于p38丝裂原活化蛋白激酶（p38MAPK）/核因子κB（NF-κB）研究微小RNA-146a（miR-146a）干预脓毒性心肌病（SIC）的分子机制。 方法 随机数字表法将SD大鼠分成四组，正常对照组、SIC模型组、miR-146a激动剂组、miR-146a抑制剂组。正常对照组、SIC模型组大鼠腹腔注射0.2 μL/g生理盐水，miR-146a激动剂组大鼠腹腔注射0.2 μL/g miR-146a激动剂、miR-146a抑制剂组大鼠腹腔注射0.2 μL/g miR-146a抑制剂；24 h后SIC模型组、miR-146a激动剂组、miR-146a抑制剂组大鼠，腹腔注射脂多糖（LPS）制备SIC大鼠模型，正常对照组注射等量生理盐水。HE染色观察组织病理学形态学；TUNEL法检测心肌细胞凋亡率；ELISA法检测心肌肌钙蛋白I（cTnI）、B型脑钠肽（BNP）含量；用化学发光法检测肌酸激酶心肌结合（CK-MB）和肌红蛋白（Mb）含量；Western blot检测大鼠心肌组织p38MAPK、NF-κB、肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）蛋白表达水平；逆转录定量（RT-q） PCR检测miR-146a 、TNF-α、白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β） mRNA水平。 结果 正常对照组大鼠心肌组织细胞大小均一，排列整齐，横纹清晰，结构正常；SIC模型组及miR-146a抑制剂组大鼠心肌细胞排列紊乱，可见心肌纤维断裂、间隔增宽；与SIC模型组相比，miR-146a激动剂组心肌结构损伤减轻。与正常对照组相比，SIC模型组、miR-146a激动剂组及miR-146a抑制剂组大鼠心肌细胞凋亡率，血清cTnI、BNP、CK-MB、Mb水平，心肌组织p-p38 MAPK、p-NF-κB p65、TNF-α、ICAM-1蛋白表达水平，TNF-α、IL-1α、IL-1β mRNA水平均明显升高，miR-146a mRNA水平降低；与SIC模型组相比，miR-146a激动剂组大鼠心肌细胞凋亡率，血清cTnI、BNP、CK-MB、Mb水平，心肌组织p-p38 MAPK、p-NF-κB p65、TNF-α、ICAM-1蛋白表达水平，TNF-α、IL-1α、IL-1β mRNA水平均明显降低，miR-146a mRNA水平升高。 结论 miR-146a可调控p38 MAPK/NF-κB信号轴，调节炎症因子的释放，miR-146a高表达对炎症反应的具有某种负向的调控，从而抑制炎症反应的发生、发展，改善炎症反应。可为SIC的早期干预治疗提供前期的机制研究以及理论支持。

Objective An exploration of the molecular mechanism of microRNA-146a （miR-146） intervention in Sepsis-induced cardiomyopathy（SIC） using P38MAPK/NF-κB. Methods SD rats were divided into four groups by the random number table method： the normal control group， the SIC model group， the miR-146a agonist group， and the miR-146a inhibitor group. Rats in the normal control group and SIC model group were injected intraperitoneally with 0.2 μL/g saline， rats in the miR-146a agonist group were injected intraperitoneally with 0.2 μL/g miR-146a agonist， rats in the miR-146a inhibitor group were injected intraperitoneally with 0.2 μL/g miR-146a inhibitor； 24 h later， rats in the SIC model group， miR-146a agonist group， and miR-146a inhibitor group were injected intraperitoneally with lipopolysaccharide （LPS） to prepare the SIC rat model， and the normal control group was injected with an equal amount of saline.Histopathological morphology was observed by HE staining； apoptosis rate of cardiomyocytes was detected by TUNEL； cardiac troponin I （cTnI） and B-type brain natriuretic peptide （BNP） contents were detected by ELISA； creatine kinase cardiac muscle binding （CK-MB） and myoglobin （Mb） contents were detected by chemiluminescence； p38 mitogen activation in rat myocardial tissue was detected by Western blot protein kinase （p38MAPK）， nuclear factor-kB （NF-κB）， tumor necrosis factor-α （TNF-α） and intercellular adhesion molecule-1 （ICAM-1） by Western-Blot； miR-146a， TNF-α， interleukin-1α （IL-1α） and interleukin-1β （IL-1β） mRNA by reverse transcription quantitative （RT-q） PCR. Results Myocardial cells in the normal control group were uniform in size， neatly arranged， with distinct transverse lines， and had normal structure； myocardial cells in the SIC model group and miR-146a inhibitor group were disordered， with myocardial fibers fragmented and expanded at intervals. Myocardial structural damage was minimized in the miR-146a agonist group compared to the SIC model group. Compared with the normal control group， the apoptosis rate， serum cTnI， BNP， CK-MB， Mb levels， myocardial tissue p-p38 MAPK， p-NF-κB p65， TNF-α， ICAM-1 protein expression levels， TNF-α， IL-1α， miR-146a mRNA levels were significantly higher in the SIC model group， miR-146a agonist group and miR-146a inhibitor group， IL-1β mRNA levels were significantly increased and miR-146a mRNA levels were decreased. Compared with the SIC model group， the apoptosis rate， serum cTnI， BNP， CK-MB， Mb levels， myocardial tissue p-p38 MAPK， p-NF-κB p65， TNF-α， ICAM-1 protein expression in the miR-146a agonist group of rats levels， TNF-α， IL-1α， IL-1β mRNA levels were significantly reduced， and miR-146a mRNA levels were increased. Conclusion miR-146a has the ability to modulate the p38 MAPK/NF-κB signaling axis and the release of inflammatory factors.High miR-146a expression has some negative influence on the inflammatory response， reducing the onset and development of the inflammatory response while improving it. It can offer SIC early intervention therapy with a pre-study mechanism and theoretical support.