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两种大鼠病态窦房结综合征建模方法:缺血再灌注和氢氧化钠损伤。

Two methods for modeling of sick sinus syndrome in rats: Ischemia reperfusion and sodium hydroxide induced injury.

机构信息

China Academy of Chinese Medicine Sciences, Xiyuan hospital, 100091, China.

Beijing University of Chinese Medicine, 100029, China.

出版信息

Biomed Pharmacother. 2019 Mar;111:778-784. doi: 10.1016/j.biopha.2018.11.091. Epub 2019 Jan 4.

Abstract

The Sick Sinus Syndrome (SSS) is a serious life-threatening heart disease. It is important to establish a credible and stable sinus node damage model. In this study, we use two methods to construct an SSS damage model in rats. One is to inject sodium hydroxide to the SSS area through internal jugular vein. Another is to cause ischemia-reperfusion injury on the SSS area. 43 healthy SD rats were randomly divided into 4 groups, namely ischemia-reperfusion injury group (IRIG), inject sodium hydroxide group (ISHG), and propranolol group (PG) and the control group (CG). The achievement ratio of modeling was 67% in the IRIG and 83% in the ISHG. The HR significantly decreased after operation in the IRIG and ISHG compared with pre-operation (P<0.01). The HR was reduced by above 30% in these 2 groups after modeling, while the reduction was better maintained in IRIG. Additionally, the sinoatrial node recovery time (SNRT) and sinoatrial conduction time (SACT) were significantly prolonged compared with pre-modeling in 2 groups (P < 0.01). Morphology results showed blurry in structure and boundaries with pale cytoplasm. It is speculated that IRIG and ISHG modeling might influence the calcium concentration and damage the sinus node function by decrease the expression of HCN4 and SCN5A, which impaired the driving ability of sinus node and leading to apoptosis. Ischemia reperfusion injury and sodium hydroxide injury could construct stable SSS models which could represent clinic pathological damage. Thus, both methods could be used for further studies of the SSS mechanisms and drugs.

摘要

病态窦房结综合征(SSS)是一种严重的危及生命的心脏病。建立一个可靠和稳定的窦房结损伤模型是很重要的。在本研究中,我们使用两种方法在大鼠中构建 SSS 损伤模型。一种是通过颈内静脉向 SSS 区域注射氢氧化钠。另一种是在 SSS 区域引起缺血再灌注损伤。43 只健康的 SD 大鼠随机分为 4 组,即缺血再灌注损伤组(IRIG)、注射氢氧化钠组(ISHG)、普萘洛尔组(PG)和对照组(CG)。IRIG 的建模成功率为 67%,ISHG 的建模成功率为 83%。与术前相比,IRIG 和 ISHG 术后 HR 明显下降(P<0.01)。建模后,这两组的 HR 下降超过 30%,而 IRIG 组的下降维持得更好。此外,与术前相比,两组的窦房结恢复时间(SNRT)和窦房结传导时间(SACT)均显著延长(P < 0.01)。形态学结果显示结构和边界模糊,胞质苍白。推测 IRIG 和 ISHG 建模可能通过降低 HCN4 和 SCN5A 的表达来影响钙浓度并损伤窦房结功能,从而降低窦房结的驱动能力并导致细胞凋亡。缺血再灌注损伤和氢氧化钠损伤可以构建稳定的 SSS 模型,能够代表临床病理损伤。因此,这两种方法都可以用于进一步研究 SSS 的机制和药物。

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