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[1]张仁鸿,陈卓,吴汉华,等.抑制乙酰转移酶p300对大鼠体外循环肺损伤及自噬的影响[J].医学研究与战创伤救治(原医学研究生学报),2025,38(01):9-15.[doi:10.16571/j.cnki.2097-2768.2025.01.002]
　ZHANG Renhong,CHEN Zhuo,WU Hanhua,et al.Effects of inhibition of acetyltransferase p300 on lung injury and autophagy during extracorporeal circulationin rats[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2025,38(01):9-15.[doi:10.16571/j.cnki.2097-2768.2025.01.002]
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抑制乙酰转移酶p300对大鼠体外循环肺损伤及自噬的影响()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
38卷
期数:
2025年01期
页码:
9-15
栏目:
论著·基础研究
出版日期:
2025-01-20

文章信息/Info

Title:
Effects of inhibition of acetyltransferase p300 on lung injury and autophagy during extracorporeal circulationin rats
文章编号:
2097-2768（2025）01-0009-07
作者:
张仁鸿; 陈卓; 吴汉华; 罗俊丽; 窦雪娇; 张红
作者单位：563006 遵义，遵义医科大学研究生院（张仁鸿、陈卓）；563099 遵义，遵义医科大学附属医院麻醉科（吴汉华、罗俊丽、窦雪娇、张红）
Author(s):
ZHANG Renhong; CHEN Zhuo; WU Hanhua; LUO Junli; DOU Xuejiao; ZHANG Hong
（1.School of Graduate，Zunyi Medical University，Zunyi 563006，Guizhou，China；2.Anesthesia Department，Affiliat?ed Hospital of Zunyi Medical University，Zunyi 563099，Guizhou，China）
关键词:
体外循环; 肺损伤; 乙酰转移酶p300; 自噬
Keywords:
cardiopulmonary bypass; lung injury; acetyltransferase p300; autophagy
分类号:
R563
DOI:
10.16571/j.cnki.2097-2768.2025.01.002
文献标志码:
A
摘要:
目的 探讨抑制乙酰转移酶p300对大鼠体外循环肺损伤及自噬的影响。方法18只雄性健康SD大鼠随机分为3组：假手术组（Sham组）、体外循环左肺损伤组（I/R组），体外循环左肺损伤+p300抑制剂组（C646组）。各6只。Sham组做穿刺及开胸处理，不建立CPB；I/R组及C646组建立CPB左肺损伤模型，并在CPB前10 min经尾静脉分别注射等量等渗盐水及p300选择性抑制剂C646；实验在3个时间点行血气分析，包括体外循环前（T1）、开放肺门10 min后（T2）以及实验结束时（T3），同时计算得出氧合指数（OI）和呼吸指数（RI）的值；T3时取左肺支气管肺泡灌洗液（BALF）及左侧肺组织，ELISA检测左肺BALF中TNF-α和总蛋白含量，透视电镜下观察左肺组织自噬小体和自噬溶酶体，Western blot检测肺组织p300及自噬相关蛋白Beclin1、p62表达。结果与Sham组比较，T2、T3时刻I/R组和C646组OI明显降低，RI明显升高（P<0.05）、TNF-α和总蛋白含量明显增加，I/R组p300和Beclin1、P62表达增加（P<0.05），C646组p300、Beclin1表达减少，p62表达增加（P<0.05），病理损伤评分明显升高（P<0.05），Ⅱ型肺泡上皮细胞胞浆内自噬明显；与I/R 组比较，T3时刻C646组OI明显升高，RI明显降低（P<0.05），TNF-α和总蛋白含量明显降低，p300和自噬相关蛋白Beclin1、P62表达减少（P<0.05），病理损伤评分明显降低，Ⅱ型肺泡上皮细胞细胞质内自噬减少（P<0.05）。结论抑制乙酰转移酶p300后大鼠CPB后肺组织自噬蛋白Beclin1、P62表达明显减少；乙酰转移酶p300 抑制剂C646可减轻肺部炎症反应，改善肺功能，可能与其抑制过度自噬有关。
Abstract:
Objective This study aims at exploring the effects of inhibition of acetyltransferase p300 on lung injury and au?tophagy during extracorporeal circulation in rats. Methods Eighteen healthy male SD rats were randomly divided into three groups（n=6）: Sham operation group（Sham group），left lung injury group after extracorporeal circulation（I/R group），extracorporeal circula?tion left lung injury + p300 inhibitor group（C646 group）. The Sham group underwent puncture and thoracotomy without establishingCPB；the I/R group and the C646 group established CPB left lung injury models，and the same amount of normal saline and the p300 se?lective inhibitor C646 were injected through the tail vein 10 min?utes before CP. Blood gas analysis was performed at three timepoints in the experiment，including before extracorporeal circulation（T1），10 minutes after opening the hilum（T2），and at the end ofthe experiment（T3）. The oxygenation index（OI）and respiratoryindex（RI）were calculated. At T3，the bronchoalveolar lavage fluid（BALF）and left lung tissue of the left lung were collected，and the TNF-αand total protein contents in the left lung BALF were detected by ELISA. The autophagosomes and autophagolysosomes of leftlung were observed under transmission electron microscope，Western-Blot detects the expression of p300 and autophagy-related pro?teins Beclin1 and p62 in lung tissue. Results Compared with the Sham group，OI was significantly decreased and RI was signifi?cantly increased in the I/R group and C646 group at T2 and T3（P<0.05）、TNF-α and total protein levels significantly increased，andthe expression of p300，Beclin1 and P62 increased in the I/R group（P<0.05）；the expression of p300 and Beclin1 decreased and theexpression of p62 increased in the C646 group（P<0.05）；the pathological damage score increased significantly（P<0.05）；autophagyis evident in the cytoplasm of type II alveolar epithelial cells. Compare with I/R group，OI was significantly increased and RI was signif?icantly decreased in the C646 group at T3（P<0.05）；TNF-α and total protein levels were significantly reduced；the expression of p300and autophagy-related proteins Beclin1 and P62 decreased（P<0.05）；the pathological damage score was significantly reduced；and au?tophagy in the cytoplasm of type II alveolar epithelial cells was reduced（P<0.05）. Conclusion After inhibiting acetyltransferasep300，the expression of autophagy proteins Beclin1 and P62 in the lung tissue of rats after CPB was significantly reduced；acetyltrans?ferase p300 inhibitor C646 can reduce pulmonary inflammatory response and improve lung function，which may be related to its inhibi?tion of excessive autophagy.

参考文献/References:

［1］ 何苗，张红.细胞凋亡在体外循环肺损伤中的研究进展［J］.医学研究生学报，2015，28（10）:1102-1106.［2］ 张元杰，吴汉华，罗俊丽，等.膜联蛋白A1拟肽Ac2-26对体外循环大鼠肺损伤及中性粒细胞凋亡的影响［J］.遵义医科大学学报，2020，43（1）:1-6.［3］ 秦莉，窦雪娇，张红，等.体外循环对大鼠肺组织细胞自噬的影响［J］.中华实验外科杂志，2023，40（8）:1508-1511.［4］ 曾祥丽，张红.乙酰转移酶p300调节细胞因子在急性肺损伤中的研究进展［J］. 医学研究生学报，2021，34（10）:1092-1096.［5］ Xu Y，Wan W. Acetylation in the regulation of autophagy［J］.Autophagy，2023，19（2）:379-387.［6］ Xu X，Li J，Long X，et al. C646 Protects Against DSS-InducedColitis Model by Targeting NLRP3 Inflammasome［J］. FrontPharmacol，2021，12（12）:707610.［7］ 刘科宇，张红，何苗，等.心脏不停跳大鼠单肺体外循环肺损伤模型的建立［J］.中国现代医学杂志，2020，30（3）:16-21.［8］ Cheng C，Li SS，Wang Y，et al. Ischemic postconditioning allevi?ates lung injury and maintains a better expression of aquaporin-1during cardiopulmonary bypass［J］.Chin Med J（Engl），2014，127（23）:4012-4018.［9］ 曹雪丽，张红.乙酰转移酶p300及其对自噬分子调控机制的研究进展［J］.医学研究生学报，2022，35（5）:549-554.［10］ Liao SX，Sun PP，Gu YH，et al. Autophagy and pulmonary dis?ease［J］. Ther Adv Respir Dis，2019，13:1-13.［11］ Shim MS，Nettesheim A，Hirt J，et al. The autophagic proteinLC3 translocates to the nucleus and localizes in the nucleolus as?sociated to NUFIP1 in response to cyclic mechanical stress［J］.Autophagy，2020，16（7）:1248-1261.［12］ Dai SH，Chen LJ，Qi WH，et al. microRNA-145 Inhibition Upreg?ulates SIRT1 and Attenuates Autophagy in a Mouse Model ofLung Ischemia/Reperfusion Injury via NF-κB-dependent Beclin1［J］.Transplantation，2021，105（3）:529-539.［13］ Liu WC，Chen SB，Liu S，et al. Inhibition of mitochondrial au?tophagy protects donor lungs for lung transplantation againstischaemia-reperfusion injury in rats via the mTOR pathway［J］.J Cell Mol Med，2019，23（5）:3190-3201.［14］ Ma X，McKeen T，Zhang J，et al. Role and Mechanisms of Mi?tophagy in Liver Diseases［J］. Cells，2020，9（4）：837.［15］ Liu Q，Yang H，Xu S，et al. Downregulation of p300 alleviates LPSinducedinflammatory injuries through regulation of RhoA /ROCK/NF-κB pathways in A549 cells［J］. Biomed Pharmacoth?er，2018，97:369-374.［16］ Chen Y，Wang D，Zhao Y，et al. p300 promotes differentiation ofTh17 cells via positive regulation of the nuclear transcription fac?tor RORγt in acute respiratory distress syndrome［J］. ImmunolLett，2018，202（76）:8-15.［17］ Wan W，You Z，Xu Y，et al. mTORC1 Phosphorylates Acetyl?transferase p300 to Regulate Autophagy and Lipogenesis［J］.Mol Cell，2017，68（2）:323-335.［18］ Qiu L，Xu C，Xia H，et al. Downregulation of P300/CBP-associat?ed factor attenuates myocardial ischemia-reperfusion injury viainhibiting autophagy［J］. Int J Med Sci，2020，17（9）: 1196-1206.［19］ Bowers EM，Yan G，Mukherjee C，et al. Virtual ligand screeningof the p300/CBP histone acetyltransferase: Identification of a se?lective small molecule inhibitor［J］. Chem Biol，2010，17（5）:471-482.

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备注/Memo

备注/Memo:
基金项目：国家自然科学基金（82060083）
更新日期/Last Update: 2025-01-20