陆军军医大学大坪医院麻醉科,重庆 400042
Received:13 November 2024,
Published:25 November 2025
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余沛,张濒丹.丙泊酚对脓毒症大鼠急性肾损伤的保护作用及机制[J].局解手术学杂志,2025,34(11):933-937.
YU Pei,ZHANG Bin-dan.Protective effect and mechanism of propofol on acute kidney injury in septic rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(11):933-937.
余沛,张濒丹.丙泊酚对脓毒症大鼠急性肾损伤的保护作用及机制[J].局解手术学杂志,2025,34(11):933-937. DOI: 10.11659/jjssx.11E024069.
YU Pei,ZHANG Bin-dan.Protective effect and mechanism of propofol on acute kidney injury in septic rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(11):933-937. DOI: 10.11659/jjssx.11E024069.
目的
2
探究丙泊酚对脓毒症大鼠急性肾损伤的保护作用及潜在机制。
方法
2
84只成年SD大鼠随机分为假手术组、模型组和治疗组。假手术组仅开关腹,模型组行盲肠结扎穿孔术建模。治疗组于建模前30 min腹腔注射丙泊酚(60 mg/kg),建模后6 h再次腹腔注射相同剂量丙泊酚。观察各组大鼠肾功能和肾病理改变,记录各组大鼠24 h内存活情况,并计算24 h存活率。通过脂多糖(LPS)刺激人肾小管上皮细胞系建立体外脓毒症模型,观察肾小管上皮细胞凋亡及氧化应激的变化;分析丙泊酚对LPS刺激后的肾小管上皮细胞氧化应激及凋亡的影响。
结果
2
脓毒症大鼠出现肾功能下降和肾组织结构破坏,大鼠24 h存活率显著下降,生存时间缩短。丙泊酚可有效改善脓毒症大鼠肾功能,降低肾Paller评分,提高大鼠存活率,延长大鼠生存时间。LPS可导致肾小管上皮细胞凋亡和细胞氧化应激,而丙泊酚可抑制肾小管上皮细胞氧化应激和细胞凋亡。
结论
2
丙泊酚可有效减轻脓毒症大鼠急性肾损伤,其机制与抑制肾小管上皮细胞凋亡和氧化应激有关。
Objective
2
To explore the protective effect and potential mechanism of propofol on acute kidney injury in septic rats.
Methods
2
A total of 84 adult SD rats were randomly divided into the sham surgery group, the model group and the treatment group. The sham surgery group only opened and closed the abdomen, while the model group underwent cecal ligation and perforation for modeling. In the treatment group, propofol (60 mg/kg) was intraperitoneally injected 30 minutes before modeling, and the same dose of propofol was intraperitoneally injected again 6 hours after modeling. The renal function and pathological changes of rats in each group were observed, 24-hour survival status of rats in each group were recorded, and the 24-hour survival rate was calculated. A sepsis model was established in vitro by stimulating human renal tubular epithelial cell line with lipopolysaccharide (LPS), and the changes of apoptosis and oxidative stress of renal tubular epithelial cells were observed. The effects of propofol on oxidative stress and apoptosis of renal tubular epithelial cells stimulated by LPS were analyzed.
Results
2
The renal function of sepsis rats was decreased, the renal tissue structure was damaged, the 24-hour survival rate of rats was decreased significantly and the survival time was shortened. Propofol could effectively improve renal function, reduce renal Paller score,increase survival rate and prolong survival time in sepsis rats. LPS could induce apoptosis and oxidative stress of renal tubular epithelial cells, while propofol could inhibit oxidative stress and apoptosis of renal tubular epithelial cells.
Conclusion
2
Propofol can effectively alleviate acute kidney injury in septic rats, and its mechanism is related to the inhibition of apoptosis and oxidative stress of renal tubular epithelial cells.
Poston JT , Koyner JL . Sepsis associated acute kidney injury [J]. BMJ , 2019 , 364 : k4891 . doi: 10.1136/bmj.k4891 http://dx.doi.org/10.1136/bmj.k4891 .
Kuwabara S , Goggins E , Okusa MD . The pathophysiology of sepsis- associated AKI [J]. Clin J Am Soc Nephrol , 2022 , 17 ( 7 ): 1050 - 1069 . doi: 10.2215/CJN.00850122 http://dx.doi.org/10.2215/CJN.00850122 .
White KC , Serpa-Neto A , Hurford R , et al . Sepsis-associated acute kidney injury in the intensive care unit:incidence,patient characteristics,timing,trajectory,treatment,and associated outcomes.A multicenter,observational study [J]. Intensive Care Med , 2023 , 49 ( 9 ): 1079 - 1089 . doi: 10.1007/s00134-023-07138-0 http://dx.doi.org/10.1007/s00134-023-07138-0 .
Han RH , Huang HM , Han H , et al . Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia [J]. Mil Med Res , 2021 , 8 ( 1 ): 58 . doi: 10.1186/s40779-021-00353-0 http://dx.doi.org/10.1186/s40779-021-00353-0 .
Tang Y , Gao X , Xu J , et al . Remimazolam besylate versus propofol for deep sedation in critically ill patients:a randomized pilot study [J]. Crit Care , 2023 , 27 ( 1 ): 474 . doi: 10.1186/s13054-023-04760-8 http://dx.doi.org/10.1186/s13054-023-04760-8 .
Fan X , Gong M , Yu H , et al . Propofol enhances stem-like properties of glioma via GABA A R-dependent Src modulation of ZDHHC5-EZH2 palmitoylation mechanism [J]. Stem Cell Res Ther , 2022 , 13 ( 1 ): 398 . doi: 10.1186/s13287-022-03087-5 http://dx.doi.org/10.1186/s13287-022-03087-5 .
Vellinga R , Hannivoort LN , Introna M , et al . Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia [J]. Br J Anaesth , 2021 , 126 ( 2 ): 386 - 394 . doi: 10.1016/j.bja.2020.10.027 http://dx.doi.org/10.1016/j.bja.2020.10.027 .
Zhou BW , Zhang WJ , Zhang FL , et al . Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4 [J]. J Transl Med , 2024 , 22 ( 1 ): 316 . doi: 10.1186/s12967-024-05107-9 http://dx.doi.org/10.1186/s12967-024-05107-9 .
Xie L , Zhao M , Zong L , et al . Propofol ameliorates sepsis-induced myocardial dysfunction via anti-apoptotic,anti-oxidative properties,and mTOR signaling [J]. Discov Med , 2024 , 36 ( 189 ): 2088 - 2097 . doi: 10.24976/Discov.Med.202436189.193 http://dx.doi.org/10.24976/Discov.Med.202436189.193 .
Bredthauer A , Geiger A , Gruber M , et al . Propofol ameliorates exaggerated human neutrophil activation in a LPS sepsis model [J]. J Inflamm Res , 2021 , 14 : 3849 - 3862 . doi: 10.2147/JIR.S314192 http://dx.doi.org/10.2147/JIR.S314192 .
Tan L , She H , Zheng J , et al . Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@ PAMAM-MR [J]. J Transl Med , 2022 , 20 ( 1 ): 591 . doi: 10.1186/s12967-022-03811-y http://dx.doi.org/10.1186/s12967-022-03811-y .
Paller MS , Hoidal JR , Ferris TF . Oxygen free radicals in ischemic acute renal failure in the rat [J]. J Clin Invest , 1984 , 74 ( 4 ): 1156 - 1164 . doi: 10.1172/JCI111524 http://dx.doi.org/10.1172/JCI111524 .
Tsuji N , Tsuji T , Yamashita T , et al . BAM15 treats mouse sepsis and kidney injury,linking mortality,mitochondrial DNA,tubule damage,and neutrophils [J]. J Clin Invest , 2023 , 133 ( 7 ): e152401 . doi: 10.1172/JCI152401 http://dx.doi.org/10.1172/JCI152401 .
Lin Q , Li S , Jiang N , et al . Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy [J]. Autophagy , 2021 , 17 ( 10 ): 2975 - 2990 . doi: 10.1080/15548627. 2020.1848971 http://dx.doi.org/10.1080/15548627.2020.1848971 .
Wang Y , Xi W , Zhang X , et al . CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway [J]. Front Immunol , 2022 , 13 : 1053754 . doi: 10.3389/fimmu.2022. 1053754 http://dx.doi.org/10.3389/fimmu.2022.1053754 .
Uchida T , Yamada M , Inoue D , et al . Involvement of innate immune system in the pathogenesis of sepsis-associated acute kidney injury [J]. Int J Mol Sci , 2023 , 24 ( 15 ): 12465 . doi: 10.3390/ijms2415 12465 http://dx.doi.org/10.3390/ijms241512465 .
Wang L , Gao X , Tang X , et al . SENP1 protects cisplatin-induced AKI by attenuating apoptosis through regulation of HIF-1α [J]. Exp Cell Res , 2022 , 419 ( 1 ): 113281 . doi: 10.1016/j.yexcr.2022.113281 http://dx.doi.org/10.1016/j.yexcr.2022.113281 .
Huang G , Bao J , Shao X , et al . Inhibiting pannexin-1 alleviates sepsis-induced acute kidney injury via decreasing NLRP3 inflammasome activation and cell apoptosis [J]. Life Sci , 2020 , 254 : 117791 . doi: 10.1016/j.lfs.2020.117791 http://dx.doi.org/10.1016/j.lfs.2020.117791 .
Zhang Q , Shen X , Yuan X , et al . Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis [J]. Nat Commun , 2024 , 15 ( 1 ): 3213 . doi: 10.1038/s41467-024-47553-5 http://dx.doi.org/10.1038/s41467-024-47553-5 .
Li J , Wang L , Wang B , et al . NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation [J]. Theranostics , 2023 , 13 ( 9 ): 2863 - 2878 . doi: 10.7150/thno.81240 http://dx.doi.org/10.7150/thno.81240 .
Su L , Zhang J , Gomez H , et al . Mitochondria ROS and mitophagy in acute kidney injury [J]. Autophagy , 2023 , 19 ( 2 ): 401 - 414 . doi: 10.1080/15548627.2022.2084862 http://dx.doi.org/10.1080/15548627.2022.2084862 .
Yu H , Jin F , Liu D , et al . ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury [J]. Theranostics , 2020 , 10 ( 5 ): 2342 - 2357 . doi: 10.7150/thno.40395 http://dx.doi.org/10.7150/thno.40395 .
Cantoni O , Zito E , Fiorani M , et al . Arsenite impinges on endoplasmic reticulum-mitochondria crosstalk to elicit mitochondrial ROS formation and downstream toxicity [J]. Semin Cancer Biol , 2021 , 76 : 132 - 138 . doi: 10.1016/j.semcancer.2021.06.002 http://dx.doi.org/10.1016/j.semcancer.2021.06.002 .
Sun P , Huang H , Ma J , et al . Repurposing propofol for breast cancer therapy through promoting apoptosis and arresting cell cycle [J]. Oncol Rep , 2024 , 52 ( 5 ): 155 . doi: 10.3892/or.2024.8814 http://dx.doi.org/10.3892/or.2024.8814 .
Xuan W , Lu X , Yang Z , et al . Propofol protects against erastin-induced ferroptosis in HT-22 cells [J]. J Mol Neurosci , 2022 , 72 ( 9 ): 1797 - 1808 . doi: 10.1007/s12031-022-02017-7 http://dx.doi.org/10.1007/s12031-022-02017-7 .
Zeng W , Xing Z , Tan M , et al . Propofol regulates activated macrophages metabolism through inhibition of ROS-mediated GLUT1 expression [J]. Inflamm Res , 2021 , 70 ( 4 ): 473 - 481 . doi: 10.1007/s00011-021-01449-y http://dx.doi.org/10.1007/s00011-021-01449-y .
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