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阿芬太尼调节SphK1/S1P信号通路对急性心肌梗死大鼠心肌纤维化的影响
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| 篇名： | 阿芬太尼调节SphK1/S1P信号通路对急性心肌梗死大鼠心肌纤维化的影响 |
| TITLE： | Effects of alfentanil on myocardial fibrosis in rats with acute myocardial infarction by regulating the SphK1/S1P signaling pathway |
| 摘要： | 目的 探究阿芬太尼（ALF）调节鞘氨醇激酶1（SphK1）/1-磷酸鞘氨醇（S1P）信号通路对急性心肌梗死（AMI）大鼠心肌纤维化的影响。方法取雄性SD大鼠，采用左冠状动脉前降支结扎法构建AMI模型，并将造模成功的大鼠随机分为AMI模型组（Model组）和低剂量ALF组（ALF-L组，予0.25mg/kgALF）、高剂量ALF组（ALF-H组，予0.5mg/kgALF）、高剂量ALF+SphK1激活剂组（ALF-H+K6PC-5组，予0.5mg/kgALF+1μg/gK6PC-5），同时设置仅进行开/关胸操作而不作左冠状动脉前降支结扎的假手术组（Sham组），每组15只。各药物组大鼠腹腔注射相应药液，每天1次，连续4周。末次给药12h后，检测各组大鼠的心功能指标[左室收缩压（LVSP）、左室射血分数（LVEF）、左室收缩期内径（LVSD）、左室短轴缩短率（LVFS）]，观察其心肌梗死情况、心肌组织病理改变和纤维化程度，检测其血清脑钠肽（BNP）、心肌肌钙蛋白Ⅰ（cTnⅠ）水平以及心肌组织中Ⅰ型胶原蛋白（collagenⅠ）、collagenⅢ、基质金属蛋白酶2（MMP-2）、SphK1、S1P蛋白的表达水平。结果与Sham组比较，Model组大鼠心肌组织细胞排列紊乱，可见大量炎症细胞浸润；LVSP、LVFS、LVEF均显著降低（P＜0.05）；LVSD，心肌梗死面积、心肌组织胶原容积分数，血清BNP、cTnⅠ水平，心肌组织中collagenⅠ、collagenⅢ、MMP-2、SphK1、S1P蛋白的表达水平均显著升高或增大（P＜0.05）。与Model组比较，ALF各剂量组大鼠心肌组织病理改变和纤维化程度均有所改善或减轻，ALF-H组大鼠各定量指标均显著改善且显著优于ALF-L组（P＜0.05）；K6PC-5可显著逆转高剂量ALF对大鼠上述各定量指标的改善作用（P＜0.05）。结论ALF可减轻AMI大鼠心肌纤维化，改善其心功能，该作用可能与抑制SphK1/S1P信号通路有关。 |
| ABSTRACT： | OBJECTIVE To explore the effects of alfentanil （ALF） on myocardial fibrosis in rats with acute myocardial infarction （AMI） by regulating sphingosine kinase 1 （SphK1）/sphingosine 1-phosphate （S1P） signaling pathway. METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery. The successfully modeled rats were randomly divided into AMI model group （Model group）， ALF low-dose group （ALF-L group， 0.25 mg/kg ALF）， ALF high-dose group （ALF-H group， 0.5 mg/kg ALF）， high dose of ALF+SphK1 activator group （ALF-H+K6PC-5 group， 0.5 mg/kg ALF+1 μg/g K6PC-5）. At the same time， a sham operation group （Sham group） was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery， with 15 rats in each group. Rats in each drug group were intraperitoneally injected with the corresponding drug solution， once a day， for 4 consecutive weeks. Twelve hours after the last medication， cardiac function indicators [left ventricular systolic pressure （LVSP）， left ventricular ejection fraction （LVEF）， left ventricular systolic diameter （LVSD）， left ventricular fractional shortening （LVFS）] of rats were detected in each group； the condition of myocardial infarction， pathological changes in myocardial tissue， and degree of fibrosis were observed； serum levels of brain natriuretic peptide （BNP） and cardiac troponin Ⅰ （cTnⅠ） in rats were detected. The protein expressions of collagen Ⅰ ， collagen Ⅲ ， matrix metalloproteinase-2 （MMP-2）， SphK1 and S1P were alsodetected in the myocardial tissue of rats. RESULTS Compared with the Sham group， the arrangement of myocardial cells in the Model group was disordered， with a large number of inflammatory cells infiltrating. The levels of LVSP， LVFS and LVEF in the Model group were significantly reduced （P＜0.05）； LVSD level， myocardial infarction area， collagen volume fraction， serum levels of BNP and cTnⅠ， the protein expressions of collagen Ⅰ， collagen Ⅲ， MMP-2， SphK1 and S1P in myocardial tissue were significantly increased or enlarged （P＜0.05）. Compared with the Model group， the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved， while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group （P＜0.05）. K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats （P＜0.05）. CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats， and the effect may be related to the inhibition of the SphK1/S1P signaling pathway. |
| 期刊： | 2024年第35卷第08期 |
| 作者： | 肖锦亮；邹雪；但家朋 |
| AUTHORS： | XIAO Jinliang，ZOU Xue，DAN Jiapeng |
| 关键字： | 阿芬太尼；急性心肌梗死；心肌纤维化；SphK1/S1P信号通路 |
| KEYWORDS： | alfentanil； acute myocardial infarction； myocardial fibrosis； SphK1/S1P signaling pathway |
| 阅读数： | 3 次 |
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