The novel mechanism of valproate to prevent peritoneal adhesion formation
The novel mechanism of valproate to prevent peritoneal adhesion formation
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丙戊酸预防腹膜粘连形成的新机制
DOI：
10.1007/s00595-020-01979-8
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发表时间：
2020-04-01
期刊：
影响因子：
2.5
通讯作者：
Takai, Shinji
中科院分区：
文献类型：
--
作者：
Liu, Shuangping;Liu, Liping;Takai, Shinji
目的利用金黄地鼠粘连模型分析丙戊酸钠的新药理作用机制。方法盲肠损伤后立即给予丙戊酸钠或安慰剂，并对粘连严重程度评分和组织学进行分析。结果安慰剂组和丙戊酸盐组的粘连严重程度评分分别为2.67 ± 0.42和1.0 ± 0.37，两组之间存在显著差异。与假手术组相比，在安慰剂给药组中观察到肥大细胞数量显著增加;然而，丙戊酸盐给药组中粘连性病变中的肥大细胞数量显著低于安慰剂给药组。安慰剂治疗组粘连性病变中糜酶（肥大细胞中的一种酶）阳性细胞数量显著较高，但丙戊酸盐治疗显著减弱了其增加。安慰剂给药组盲肠中的髓过氧化物酶基因表达水平显著高于假手术组，但假手术组和丙戊酸盐给药组之间的髓过氧化物酶基因表达水平无显著差异。在体外实验中，丙戊酸盐以剂量依赖性方式抑制纯化的人和仓鼠糜酶。结论丙戊酸钠对糜酶的抑制作用可能有助于防止腹部创伤后粘连的形成。
Purpose A novel pharmacological mechanism of valproate was analyzed using a hamster model of adhesion. Methods Valproate or placebo was administered just after cecal injury and adhesion severity scores and histological were analyzed. Results The adhesion severity scores in the placebo- and valproate-treated groups were 2.67 +/- 0.42 and 1.0 +/- 0.37, respectively, with a significant difference between the groups. A significant increase in mast cell numbers was observed in the placebo-treated group vs. the sham-operated group; however, the mast cell number in the adhesive lesion was significantly lower in the valproate-treated group than in the placebo-treated group. The number of cells positive for chymase, an enzyme in mast cells, in the adhesive lesion was significantly higher in the placebo-treated group, but its increase was attenuated significantly by treatment with valproate. The myeloperoxidase gene expression level in the cecum was significantly higher in the placebo-treated group than in the sham-operated group, but there was no significant difference in the myeloperoxidase gene expression level between the sham-operated and valproate-treated groups in. In an in vitro experiment, valproate inhibited purified human and hamster chymases dose-dependently. Conclusion The chymase inhibitory effect of valproate may contribute to prevent adhesion formation after abdominal injury.