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神经介入输注血红蛋白氧载体可预防大鼠急性脑缺血所致脑损伤。

Neurointerventional infusion of hemoglobin oxygen carrier prevents brain damage from acute cerebral ischemia in rats.

作者信息

Gao Hong, Peng Han, Yang Hua, Li Qiuping, Xiang Xin

机构信息

Department of Neurosurgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.

Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

出版信息

Front Surg. 2023 Mar 3;10:1050935. doi: 10.3389/fsurg.2023.1050935. eCollection 2023.

DOI:10.3389/fsurg.2023.1050935
PMID:36936654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10020359/
Abstract

AIM

To save brain cells in acute cerebral infarction by injecting hemoglobin oxygen carrier (HBOC) into the blood vessel blockage of the cerebral infarction site through a microcatheter.

METHODS

120 male rats were divided into four groups: control (CTRL), ischemia (I), ischemia + low perfusion (I + LP), and ischemia + high perfusion (I + HP). Perfusion groups (ischemia, I + LP, and I + HP) underwent MCAO surgery with intraluminal monofilament. These groups were subdivided into 6 h, 12 h, and 24 h ( = 10/group). RT-PCR, Western-Blot, immunohistochemistry, and apoptosis assays were used to detect apoptosis, hypoxia range and extent, and ischemia.

RESULTS

Compared with the I group, the neurological deficit sign scores of the I + HP group were statistically significant at 12 h. Compared with the I group, the neurological deficit sign scores of the I + LP group and the I + HP group were statistically significant at 24 h. At all time points, compared with the I group and the I + LP group, Caspase-3, HIF-1α, and Cytochrome C protein levels were significantly decreased in the I + HP group. Bcl-2 and BAX mRNA levels were also significantly decreased in the same group. TNF-α, IL-6, and IL-1β cytokines were significantly decreased in the I + HP group as well. The infarct size of rats in the I + HP group was smaller than that of the I + LP group, which was smaller than ischemia alone. Time of perfusion had an obvious effect as infarct size was smaller with longer perfusion. The number of Nissl stained cells in the I + HP group was increased compared with the ischemia and the I + LP group, and was proportional to the time of perfusion.

CONCLUSION

Time- and rate-controlled perfusion of HBOC to acutely occluded cerebral vascular regions through microcatheters can effectively protect ischemic brain tissue in rats.

摘要

目的

通过微导管将血红蛋白氧载体(HBOC)注入脑梗死部位的血管堵塞处,以挽救急性脑梗死中的脑细胞。

方法

将120只雄性大鼠分为四组:对照组(CTRL)、缺血组(I)、缺血+低灌注组(I+LP)和缺血+高灌注组(I+HP)。灌注组(缺血组、I+LP组和I+HP组)采用腔内单丝法进行大脑中动脉闭塞(MCAO)手术。这些组再细分为6小时、12小时和24小时组(每组n=10)。采用逆转录-聚合酶链反应(RT-PCR)、蛋白质免疫印迹法(Western-Blot)、免疫组织化学和凋亡检测来检测细胞凋亡、缺氧范围和程度以及缺血情况。

结果

与I组相比,I+HP组在12小时时神经功能缺损体征评分具有统计学意义。与I组相比,I+LP组和I+HP组在24小时时神经功能缺损体征评分具有统计学意义。在所有时间点,与I组和I+LP组相比,I+HP组中半胱天冬酶-3(Caspase-3)、缺氧诱导因子-1α(HIF-1α)和细胞色素C蛋白水平显著降低。同一组中Bcl-2和BAX mRNA水平也显著降低。I+HP组中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)细胞因子也显著降低。I+HP组大鼠的梗死面积小于I+LP组,I+LP组小于单纯缺血组。灌注时间有明显影响,灌注时间越长梗死面积越小。与缺血组和I+LP组相比,I+HP组中尼氏染色细胞数量增加,且与灌注时间成正比。

结论

通过微导管对急性闭塞脑血管区域进行时间和速率控制的HBOC灌注可有效保护大鼠缺血脑组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/35a223f507ae/fsurg-10-1050935-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/c4ac40c10a47/fsurg-10-1050935-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/15836b8ab655/fsurg-10-1050935-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/35a223f507ae/fsurg-10-1050935-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/c4ac40c10a47/fsurg-10-1050935-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/15836b8ab655/fsurg-10-1050935-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/10020359/35a223f507ae/fsurg-10-1050935-g008.jpg

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