丙戊酸钠对重度烫伤大鼠肺微血管内皮屏障的保护作用和机制研究

张文华; 唐富波; 胡森; 杜明华

doi:10.3969/j.issn.2095-5227.2021.10.012

丙戊酸钠对重度烫伤大鼠肺微血管内皮屏障的保护作用和机制研究

Protective effect and mechanism of sodium valproate on pulmonary microvascular endothelial barrier in severely scalded rats

摘要

摘要:
背景严重烧伤后患者出现全身炎症反应综合征，可引起毛细血管渗漏症，最终导致多器官功能障碍，严重影响预后。组蛋白乙酰化在毛细血管渗漏的进展过程中发挥重要作用。丙戊酸钠作为去乙酰化的抑制剂，可能保护烧伤患者器官功能。
目的研究组蛋白去乙酰化酶抑制剂丙戊酸钠(valproic acid，VPA)对烫伤大鼠肺微血管内皮屏障的保护作用及其机制。
方法 SD大鼠随机分为假烫+0.9%氯化钠注射液组(NN组)、假烫+VPA组(NV组)、烫伤+0.9%氯化钠注射液组(SN组)、烫伤+VPA组(SV组)，每组16只。分别于伤后2 h和6 h处死大鼠。取肺组织测定肺微血管通透性、组织含水率和血管内皮生长因子(vascular endothelial growth factor，VEGF)含量、髓过氧化物酶(myeloperoxidase，MPO)活性和组蛋白H3K9位赖氨酸的乙酰化(Ac-H3K9)水平。
结果与NN组相比，SN组2 h和6 h大鼠肺微血管通透性和肺组织含水率均显著增加(P均＜ 0.05)；同时VEGF水平、MPO活性及Ac-H3K9表达也明显增高。伤后6 h，与SN组相比，SV组大鼠肺微血管通透性降低，肺组织含水率减少，VEGF水平、MPO活性、Ac-H3K9表达降低(P均＜ 0.05)。
结论 VPA可显著减轻严重烫伤引起的肺微血管内皮屏障损害，其作用机制可能与丙戊酸钠对VEGF和MPO的抑制作用有关。

Abstract:
Background Patients are prone to have a systemic inflammatory response syndrome (SIRS) after severe burns. SIRS can cause capillary leakage, and lead to multiple organ dysfunction, which seriously affects the prognosis. Histone acetylation plays an important role in the progression of capillary leakage. As an inhibitor of deacetylation, sodium valproate may protect the organ in burnt patients.
Objective To investigate the protective effect and mechanism of histone deacetylase inhibitors called VPA on microvascular endothelial barrier in rats after severe burn injury.
Methods Rats were randomly divided into four groups: normal+0.9% NaCl normal saline (NN group), normal+VPA (NV group), scald+0.9% NaCl normal saline (SN group), scald+VPA (SV group) with 16 rats in each group. Rats were sacrificed at 2 h and 6 h after injury. Pulmonary microvascular permeability, tissue water content, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO) activity and acetylation of histone H3K9 lysine (Ac-H3K9) were detected in lung tissues.
Results Compared with the NN group, lung microvascular permeability and lung tissue moisture content increased significantly in the SN group at 2 h and 6 h (all P < 0.05) ; At the same time, the level of VEGF, the activity of MPO, and the expression of Ac-H3K9 also significantly increased (all P < 0.05). However, compared with SN group, they all decreased in the SV group at 6 h after injury (all P < 0.05).
Conclusion VPA can reduce the damage of pulmonary micro-vascular endothelial barrier caused by severe scald, and its mechanism may be related to the inhibitory effect on VEGF and MPO.

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