在伴有急性肾损伤的脓毒性休克大鼠模型中,血管紧张素II通过AMPK/PGC-1α/NRF-2途径介导的肾线粒体功能改善作用优于去甲肾上腺素。
Angiotensin II-mediated improvement of renal mitochondrial function via the AMPK/PGC-1α/NRF-2 pathway is superior to norepinephrine in a rat model of septic shock associated with acute renal injury.
作者信息
An Hui, Hu Zhenjie, Chen Yuhong, Cheng Lianfang, Shi Jian, Han Linan
机构信息
Department of Intensive Care Unit, Hebei Medical University, Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China.
Department of Intensive Care Unit, Baoding First Central Hospital, Baoding, China.
出版信息
Ann Transl Med. 2021 Mar;9(6):481. doi: 10.21037/atm-21-621.
BACKGROUND
This study sought to compare the therapeutic effects of angiotensin II (ANG II) and norepinephrine (NE) on cecal ligation and puncture (CLP)-induced septic acute kidney injury (AKI) in rats.
METHODS
Sepsis shock was induced in anesthesia Sprague-Dawley male rats by CLP model for 24 hours. A total of 40 rats were divided into five groups, including control group, sham group, CLP group, CLP + ANG II group, and CLP + NE group. CLP + ANG II and CLP + NE group were administration of ANG II or NE after sepsis shock respectively, maintaining the MAP at 75-85 mmHg. CLP group was administration of saline for contrast. At 0, 18, 24 hours measured the renal blood grades and resistant index (RI) by ultrasound equipment. At 6, 12, 18 and 24 hours collected 0.5 mL blood sample for creatinine and lactic acid examination. Rats were observed for 24 hours after CLP procedure and then sacrificed for subsequent examination, rat serum were used to determine the levels of inflammatory response factors, kidney tissues were used to examine the oxidative stress factors and mitochondrial related proteins." We added the sentence as following: "The AMPK, PGC-1α and NRF-2 expression in renal cortex was significantly increased in the CLP + ANG II group.
RESULTS
Compared to the vehicle treatment, both ANG II and NE administration restored the decrease in the mean arterial pressure (MAP) and alleviated mitochondrial impairments in CLP rats. However, only ANG II alleviated CLP-induced abnormalities in serum creatinine and lactic acid concentrations, renal blood flow, the renal resistant index, renal histopathology, the production of proinflammatory cytokines, and oxidative stress markers in rats. ANG II was also found to be superior to NE in reversing the CLP-induced suppression of mitochondrial biogenesis-related protein expression in the kidneys of rats.
CONCLUSIONS
ANG II was better than NE in alleviating CLP-induced septic AKI in rats.
背景
本研究旨在比较血管紧张素II(ANG II)和去甲肾上腺素(NE)对盲肠结扎穿刺(CLP)诱导的大鼠脓毒症急性肾损伤(AKI)的治疗效果。
方法
采用CLP模型在麻醉的Sprague-Dawley雄性大鼠中诱导脓毒症休克24小时。总共40只大鼠分为五组,包括对照组、假手术组、CLP组、CLP + ANG II组和CLP + NE组。CLP + ANG II组和CLP + NE组分别在脓毒症休克后给予ANG II或NE,将平均动脉压(MAP)维持在75 - 85 mmHg。CLP组给予生理盐水作为对照。在0、18、24小时用超声设备测量肾血流分级和阻力指数(RI)。在6、12、18和24小时采集0.5 mL血样进行肌酐和乳酸检测。CLP术后观察大鼠24小时,然后处死进行后续检查,用大鼠血清测定炎症反应因子水平,用肾组织检测氧化应激因子和线粒体相关蛋白。我们补充了如下句子:CLP + ANG II组肾皮质中AMPK、PGC - 1α和NRF - 2表达显著增加。
结果
与载体治疗相比,ANG II和NE给药均恢复了CLP大鼠平均动脉压(MAP)的降低并减轻了线粒体损伤。然而,只有ANG II减轻了CLP诱导的大鼠血清肌酐和乳酸浓度异常、肾血流量、肾阻力指数、肾组织病理学、促炎细胞因子产生和氧化应激标志物异常。还发现ANG II在逆转CLP诱导的大鼠肾脏线粒体生物发生相关蛋白表达抑制方面优于NE。
结论
在减轻CLP诱导的大鼠脓毒症AKI方面,ANG II优于NE。