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在实验小鼠模型中评估抗前蛋白转化酶枯草溶菌素9(PCSK9)疫苗对全身炎症和氧化应激的影响。

Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in an experimental mouse model.

作者信息

Momtazi-Borojeni Amir Abbas, Banach Maciej, Sahebkar Amirhossein

机构信息

Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Department of Medical Biotechnology, School of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran.

出版信息

Cardiol J. 2025;32(1):73-82. doi: 10.5603/cj.100585. Epub 2025 Jan 8.

DOI:10.5603/cj.100585
PMID:39776050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11870013/
Abstract

BACKGROUND

To investigate whether the antiPCSK9 vaccine can affect the CRP and oxidative stress (OS) during acute systemic inflammation.

METHODS

Male albino mice were randomly divided into three groups: non-treated mice (the sham group), treated with a nonspecific stimulator of the immune response - Freund's complete adjuvant (CFA; the CFA group), and vaccinated mice treated with CFA (the vaccine group). The vaccine group was subcutaneously immunized with the antiPCSK9 formulation, 4 × in bi-weekly intervals. To induce inflammation, all mice were subjected to the CFA challenge after the vaccination plan. The hsCRP level and OS status were evaluated by a mouse CRP ELISA kit and the pro-oxidant antioxidant balance (PAB) assay, respectively.

RESULTS

The vaccine induced a high-titter IgG antiPCSK9 antibody, which was accompanied with a significant PCSK9 reduction (-24.7% and -28.5% compared with the sham and CFA group, respectively), and the inhibition of PCSK9/LDLR interaction (-27.8% and -29.4%, respectively). hsCRP was significantly increased in the vaccine and CFA groups by 225% and 274% respectively, when compared with the sham group; however, it was non-significantly decreased (-18%; p = 0.520) in the vaccine group in comparison with the CFA group. The PAB values indicated that OS was significantly increased in the CFA group (by 72.7%) and the vaccine group (by 76%) when compared to the sham group; however, there was no significant difference in the PAB values between the vaccine and CFA groups.

CONCLUSION

The antiPCSK9 vaccine failed to significantly reduce the serum hs-CRP and OS induced in the CFA-challenged albino mice.

摘要

背景

研究抗PCSK9疫苗在急性全身炎症期间是否会影响C反应蛋白(CRP)和氧化应激(OS)。

方法

将雄性白化小鼠随机分为三组:未处理小鼠(假手术组)、用免疫反应非特异性刺激剂——弗氏完全佐剂(CFA;CFA组)处理的小鼠以及用CFA处理的接种疫苗小鼠(疫苗组)。疫苗组每两周皮下免疫一次抗PCSK9制剂,共4次。为诱导炎症,所有小鼠在疫苗接种计划后接受CFA攻击。分别用小鼠CRP ELISA试剂盒和促氧化剂抗氧化剂平衡(PAB)测定法评估高敏CRP水平和OS状态。

结果

该疫苗诱导产生高滴度IgG抗PCSK9抗体,同时PCSK9显著降低(分别比假手术组和CFA组降低24.7%和28.5%),并且PCSK9/LDLR相互作用受到抑制(分别为27.8%和29.4%)。与假手术组相比,疫苗组和CFA组的hsCRP分别显著升高225%和274%;然而,与CFA组相比,疫苗组hsCRP无显著降低(降低18%;p = 0.520)。PAB值表明,与假手术组相比,CFA组(升高72.7%)和疫苗组(升高76%)的OS显著增加;然而,疫苗组和CFA组的PAB值无显著差异。

结论

抗PCSK9疫苗未能显著降低CFA攻击的白化小鼠中诱导产生的血清高敏CRP和OS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/ae811ea43f65/cardj-32-1-73f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/93e3165561ea/cardj-32-1-73f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/abce1d51588c/cardj-32-1-73f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/ae811ea43f65/cardj-32-1-73f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/93e3165561ea/cardj-32-1-73f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/abce1d51588c/cardj-32-1-73f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c3/11870013/ae811ea43f65/cardj-32-1-73f3.jpg

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