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载色蛋白 A N 端片段血管抑肽-1 纳米载体转染对腹主动脉瘤形成的影响。

Effect of chromogranin A N-terminal fragment vasostatin-1 nano-carrier transfection on abdominal aortic aneurysm formation.

机构信息

Department of Cardiovascular Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, China.

出版信息

Bioengineered. 2021 Dec;12(2):11018-11029. doi: 10.1080/21655979.2021.2005222.

Abstract

The effects of transfection of N-terminal fragment of chromogranin A Vasostatin-1 (VS-1) nanocarriers on formation of abdominal aortic aneurysm (AAA) were discussed, and its mechanism was analyzed. Nanoparticles containing VS-1 genes were prepared by emulsion solvent evaporation method, and property of nanoparticles was examined. A total of 30 male SD rats were divided randomly into sham group (normal saline), AAA group (Type I porcine pancreatic elastase), and VS-1 group (Type I porcine pancreatic elastase+VS-1 suspension liquid). The diameter dilation of rats was measured, abdominal aortic morphology was observed by HE staining, and levels of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were examined by immunohistochemistry and Western blot. Correlation between AMPK as well as mTOR and diameter dilation was analyzed by Pearson correlation. VS-1 genes in VS-1 nanoparticles were 4.51% and coating efficiency of genes was 88%. Compared with rats in sham group, diameter dilation of rats in AAA group increased, damage of abdominal aorta in rats was obvious, p-AMPK decreased, and p-mTOR increased in AAA group. Compared with AAA group, diameter dilation of rats in VS-1 group decreased, abdominal aorta of rats was improved, p-AMPK increased, and p-mTOR decreased. The comparison of all above indicators had statistical meaning ( < 0.05). p-AMPK and p-mTOR were negatively ( = -0.9150 and = 0.006) and positively correlated with the diameter dilation ( = -0.9206 and = 0.001). VS-1 nanoparticles could inhibit the formation of AAA, which might be related to the activation of AMPK/mTOR signal path.

摘要

探讨了载有嗜铬粒蛋白 A N 端片段血管抑肽-1(VS-1)纳米载体的转染对形成腹主动脉瘤(AAA)的影响,并分析了其机制。采用乳化溶剂蒸发法制备含 VS-1 基因的纳米颗粒,并对纳米颗粒的性质进行了考察。将 30 只雄性 SD 大鼠随机分为假手术组(生理盐水)、AAA 组(I 型猪胰弹性蛋白酶)和 VS-1 组(I 型猪胰弹性蛋白酶+VS-1 混悬液)。测量大鼠的直径扩张,HE 染色观察腹主动脉形态,免疫组化和 Western blot 检测 AMP 激活蛋白激酶(AMPK)和哺乳动物雷帕霉素靶蛋白(mTOR)的水平。采用 Pearson 相关性分析 AMPK 和 mTOR 与直径扩张的相关性。VS-1 纳米颗粒中的 VS-1 基因为 4.51%,基因包封率为 88%。与假手术组大鼠相比,AAA 组大鼠的直径扩张增加,大鼠腹主动脉损伤明显,p-AMPK 降低,AAA 组 mTOR 升高。与 AAA 组相比,VS-1 组大鼠的直径扩张减少,大鼠腹主动脉改善,p-AMPK 增加,p-mTOR 减少。上述所有指标的比较均有统计学意义( < 0.05)。p-AMPK 和 p-mTOR 与直径扩张呈负相关( = -0.9150 和 = 0.006)和正相关( = -0.9206 和 = 0.001)。VS-1 纳米颗粒可抑制 AAA 的形成,可能与激活 AMPK/mTOR 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fca/8810023/bb69ae6fe12c/KBIE_A_2005222_F0001_OC.jpg

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