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通过在自发性高血压大鼠中结扎冠状动脉,可以建立一种新的心肾综合征动物模型。

A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats.

机构信息

Department of Emergency Medicine, The Sixth Medical Center of Chinese PLA General Hospital, NO 6 of Fucheng Road, District of Haidian, Beijing, 100048, China.

Department of Cardiovascular Surgery, The First Medical Center of Chinese PLA General Hospital, NO 28 of Fuxing Road, District of Haidian, Beijing, 100853, China.

出版信息

Sci Rep. 2024 Aug 12;14(1):18732. doi: 10.1038/s41598-024-69662-3.

DOI:10.1038/s41598-024-69662-3
PMID:39134654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11319483/
Abstract

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin-angiotensin-aldosterone system.

摘要

在单侧肾切除和心功能障碍的大鼠中,肾功能恶化速度加快,表现为蛋白尿增加。心肌梗死引起的心力衰竭(HF)是否会加重伴有轻度肾功能损伤的高血压大鼠的肾脏损伤尚未报道。大鼠接受冠状动脉结扎或假手术。30 只 8 周龄自发性高血压大鼠(SHR)随机分为两组。第 1 组为假手术组,大鼠行开胸术,但不结扎冠状动脉。第 2 组行冠状动脉结扎术。第 2 组大鼠在第 0 周行冠状动脉结扎术。实验持续 12 周。在 24 小时期间,通过代谢笼收集尿液。在实验结束前 2 天收集大鼠的尿液,并在临床实验室测量尿液蛋白与尿液肌酐的比值。所有大鼠在实验结束前一天通过超声心动图进行检查。在实验的最后一天,采集血液并送往实验室进行分析。对心脏和肾脏切片进行苏木精-伊红(HE)和过碘酸希夫(PAS)染色。第 2 组的射血分数低于第 1 组(P<0.001)。第 2 组的尿白蛋白与尿肌酐比值大于第 1 组(P<0.001)。第 1 组的尿素和肌酐水平明显低于第 2 组(P<0.01)。第 2 组的脑钠肽(BNP)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和胱抑素 C 水平高于第 1 组(P<0.05)。第 2 组的白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平明显高于第 1 组(P<0.001)。第 2 组的丙二醛(MDA)水平高于第 1 组(P<0.01)。第 2 组的谷胱甘肽过氧化物酶(GSH-Px)水平低于第 1 组(P<0.05)。第 1 组的血管紧张素 II(AT-II)水平低于第 2 组(P<0.001)。心肌梗死引起的心脏功能障碍可在 SHR 中引起心肾相互作用。这可以通过氧化应激的激活、炎症的变化和肾素-血管紧张素-醛固酮系统的改变来解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/b52b89c86d86/41598_2024_69662_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/3cf249966874/41598_2024_69662_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/b52b89c86d86/41598_2024_69662_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/3cf249966874/41598_2024_69662_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/6cad12cdda2d/41598_2024_69662_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88d/11319483/c65d9d908286/41598_2024_69662_Fig3_HTML.jpg
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