| 袁瑶薇,王文宇,白秀萍,王晓慧,张 博.人参皂苷Rg3通过调节自噬减轻脓毒症心肌损伤[J].现代生物医学进展英文版,2022,(8):1419-1423. |
| 人参皂苷Rg3通过调节自噬减轻脓毒症心肌损伤 |
| Ginsenoside Rg3 Alleviates Myocardial Impairment via Autophagy in Sepsis |
| Received:September 22, 2021 Revised:October 23, 2021 |
| DOI：10.13241/j.cnki.pmb.2022.08.004 |
| 中文关键词: 人参皂苷Rg3 脓毒症 自噬 NLRP3炎性小体 |
| 英文关键词: Ginsenoside Rg3 Sepsis Autophagy NLRP3 inflammasome |
| 基金项目:黑龙江省中医药科研项目（ZHY2020-171；ZHY2020-172）；黑龙江省青年科学基金项目（QC2016106） |
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| 中文摘要: |
| 摘要 目的：探讨人参皂苷Rg3（ginsenoside Rg3，Rg3）对脓毒症介导的心肌损伤的作用效果及机制。方法：本研究通过对小鼠进行盲肠结扎穿孔手术的方法构建脓毒症模型。32只BALB/c小鼠随机分为假手术组（Sham组）、脓毒症组（CLP组）、人参皂苷Rg3治疗组（Rg3+CLP组）以及自噬抑制剂干预组（3-MA+Rg3+CLP组），每组8只。术后18 h分别留取各组小鼠血浆及心肌组织。通过ELISA方法检测白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）、乳酸脱氢酶（LDH）、肌酸激酶同工酶MB（CK-MB）及半胱氨酸蛋白酶-3（Caspase-3）表达水平。通过HE染色观察心肌组织形态结构的变化。应用Western-blot方法检测自噬及NLRP3炎性小体相关蛋白（NLRP3、ASC、Caspase-1）的表达。结果：与Sham组相比，CLP组小鼠心肌组织结构紊乱，炎性细胞浸润明显。另外，Caspase-3活性增加，NLRP3炎性小体相关蛋白（NLRP3、ASC、Caspase-1）表达升高，差异均有统计学意义（P＜0.05）。与CLP组相比，外源应用Rg3组小鼠心肌组织炎性细胞浸润减少，并且Caspase-3活性降低，NLRP3炎性小体相关蛋白表达下降，差异有统计学意义（P＜0.05），而部分自噬相关蛋白表达升高。应用自噬抑制剂后，较单纯应用Rg3组，心肌组织损伤明显，而NLRP3炎性小体活性增加，差异有统计学意义（P＜0.05）。结论：脓毒症时NLRP3炎性小体激活，释放大量的细胞因子，进而导致心肌损伤。而Rg3治疗后，可以调节心肌细胞自噬，抑制NLRP3炎性小体激活，进而减轻细胞因子对心肌细胞的损伤。本研究表明Rg3可能通过调节心肌自噬，抑制NLRP3炎性小体的激活，进而减轻脓毒症时心脏的损伤。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects and mechanism of ginsenoside Rg3 (Rg3) on sepsis mediated myocardial injury. Methods: In this study, sepsis models were constructed by cecal ligation and perforation (CLP). 32 BALB/c mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group), ginsenoside Rg3 treatment group (Rg3+CLP group) and autophagy inhibitor intervention group (3-MA+Rg3+CLP group), with 8 mice in each group. Plasma and myocardial tissue were collected 18 h after operation. The expression levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB) and cysteine protease-3 (Caspase-3) were detected by ELISA. Our research group observed the changes in the morphological structures of myocardial tissue by HE staining and detected the expression of autophagy and NLRP3 inflammasome associated proteins (NLRP3, ASC, Caspase-1) by Western-blot method. Results: Compared with Sham group, the myocardial tissue structures of mice in CLP group were disorganized, and inflammatory cell infiltration was obvious. In addition, Caspase-3 activity and the expression levels of NLRP3 inflammasome associated proteins (NLRP3, ASC, Caspase-1) were increased (P<0.05). Compared with CLP group, inflammatory cell infiltration in myocardial tissue of mice in Rg3+CLP group was reduced. Moreover, Caspase-3 activity and the expression levels of NLRP3 inflammasome associated proteins were decreased (P<0.05), while the expression levels of some autophagy associated proteins were increased. After the application of autophagy inhibitor, compared with Rg3+CLP group, the myocardial injury was more obvious, and the NLRP3 inflammasome activity was increased(P<0.05). Conclusion: In sepsis, NLRP3 inflammasome is activated, releasing large amounts of cytokines, which in turn leads to myocardial injury. After treatment of Rg3, it can regulate the autophagy of cardiomyocytes and inhibit the activation of NLRP3 inflammasome, thereby reducing the injury of cardiomyocytes by cytokines. This study suggests that Rg3 may inhibit the activation of NLRP3 inflammasome by regulating the autophagy of cardiomyocytes, thereby alleviating myocardial injury in sepsis. |
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