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| 雷帕霉素通过抑制mTOR上调线粒体自噬保护脓毒症大鼠下丘脑 |
| Rapamycin alleviates hypothalamic injury in septic rats by inhibiting mTOR and activating mitophagy |
| 投稿时间：2024-10-15 修订日期：2024-10-15 |
| DOI： |
| 中文关键词: 脓毒症 下丘脑 雷帕霉素 mTOR 线粒体自噬 |
| 英文关键词: Sepsis Hypothalamus Rapamycin mTOR Mitophagy |
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| 中文摘要: |
| 目的：探讨雷帕霉素（Rapa）保护脓毒症大鼠下丘脑的作用机制。方法：将60只健康雄性SD大鼠随机分为四组：假手术组（Sham）、雷帕霉素组（Rapa）、脓毒症组（Sepsis）以及脓毒症+雷帕霉素预处理组（Sepsis+Rapa），每组含15只大鼠。经4天腹腔雷帕霉素注射后，采用盲肠结扎穿孔（CLP）的方法建立脓毒症模型。随后，绘制大鼠的生存曲线，通过HE染色和尼氏染色技术观察下丘脑的组织病理学变化。利用ELISA技术测定下丘脑组织中活性氧（ROS）和丙二醛（MDA）的含量；原位末端转移酶标记法观察大鼠下丘脑组织凋亡；Western blot方法测定大鼠下丘脑组织中p-mTOR、mTOR、P62和LC3的表达，并计算LC3II/LC3I比值；免疫荧光检测下丘脑中LC3与Tom20的共定位。结果：与脓毒症组相比，雷帕霉素提高脓毒症大鼠的生存率，减轻脓毒症大鼠下丘脑病理损伤和细胞凋亡，减少下丘脑组织的ROS和MDA的水平。Western-blot和免疫荧光结果显示，雷帕霉素下调脓毒症大鼠下丘脑组织中mTOR和p62的水平，增加LC3II/LC3I比值，增强LC3和Tom20在下丘脑组织中的相互结。结论：雷帕霉素通过抑制mTOR信号通路，上调线粒体自噬，减轻脓毒症对下丘脑的损伤，有效保护下丘脑。 |
| 英文摘要: |
| Objective: To explore the mechanism by which rapamycin (Rapa) alleviates hypothalamic injury in septic rats. Methods: Forty healthy male SD rats were randomly divided into a sham operation group (Sham group), a rapamycin group (Rapa group), a sepsis group (Sepsis group), and a sepsis + rapamycin intervention group (Sepsis + Rapa group), with 10 rats in each group. After 4 days of intraperitoneal injection of rapamycin, a sepsis model was established using the cecal ligation and puncture (CLP) method. The survival curve of the rats was plotted; hypothalamic tissue was collected for HE and Nissl staining to observe histopathological changes; the levels of ROS and MDA in hypothalamic tissue were detected using the ELISA method; in situ terminal deoxynucleotidyl transferase labeling was used to observe apoptosis in the hypothalamic tissue; Western blot was used to determine the expression of pmTOR, mTOR, P62, and LC3 in the hypothalamic tissue, and the LC3II/LC3I ratio was calculated; immunofluorescence was used to detect the colocalization of LC3 and Tom20 in the hypothalamic tissue. Results: Compared with the sepsis group, rapamycin increased the survival rate of septic rats, alleviated hypothalamic pathological damage and cell apoptosis, and reduced the levels of ROS and MDA in the hypothalamic tissue. Western blot and immunofluorescence results showed that rapamycin downregulated the levels of mTOR and P62 in the hypothalamic tissue of septic rats, increased the LC3II/LC3I ratio, and enhanced the colocalization between LC3 and Tom20 in the hypothalamic tissue. Conclusions: Rapamycin alleviates sepsis-induced neuronal injury in the hypothalamus and protects hypothalamic function by inhibiting the mTOR pathway and activating mitophagy.
Key words: Sepsis; Hypothalamus; Rapamycin; mTOR; Mitophagy; |
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