| 陈 炯,于合国,徐 凌,贾蓉蓉,王玉刚,施 敏.PH797804对小鼠急性肝衰竭的保护作用及机制研究[J].,2020,(15):2801-2807 |
| PH797804对小鼠急性肝衰竭的保护作用及机制研究 |
| Protective Effect and Mechanism of PH797804 on Acute Liver Failure in Mice |
| 投稿时间：2020-02-28 修订日期：2020-03-24 |
| DOI：10.13241/j.cnki.pmb.2020.15.001 |
| 中文关键词: PH797804 急性肝衰竭 细胞因子 炎症 |
| 英文关键词: PH797804 Acute liver failure Cytokine Inflammation |
| 基金项目:国家自然科学基金面上项目（81871912; 81970530）；上海市医学重点专科（ZK2019C012） |
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| 中文摘要: |
| 摘要 目的：研究PH797804对脂多糖/D-氨基半乳糖氨（Lipopolysaccharide/D-galactosamine, LPS/D-Gal）诱导的急性肝衰竭（Acute liver failure, ALF）小鼠的保护作用及机制。方法：将64只小鼠随机分成四组，每组16只。腹腔注射LPS/D-Gal诱导建立小鼠ALF模型，设立生理盐水对照组（a）、LPS/D-Gal诱导模型组（b）、LPS/D-Gal诱导和PH797804干预组（c）及PH797804处理对照组（d）。观察小鼠48 h内的存活率，检测血清中谷丙转氨酶（ALT）和谷草转氨酶（AST）的含量，HE染色组织切片观察肝脏病理变化，Elisa检测血清中TNF-α和IL-6的表达水平，并对各组小鼠肝组织进行高通量转录组测序以探寻作用机制，采用Real-time PCR法验证测序结果。结果：相比于ALF模型组小鼠，PH797804处理后c组小鼠48 h存活率从20 %提高至80 %，小鼠肝脏组织病理学异常显著改善，血清中ALT、AST含量较ALF模型组相比显著降低（P＜0.01），血清中TNF-α和IL-6等促炎细胞因子含量较ALF模型组相比显著降低（P＜0.01）。RNA测序结果提示PH797804对LPS/D-Gal诱导小鼠ALF的保护作用主要与抑制炎症反应相关。Real-time PCR验证了测序结果的可靠性。结论：PH797804对LPS/D-Gal诱导的小鼠ALF具有保护作用，其作用机制可能与抑制炎症反应有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the protective effect and mechanism of PH797804 on Lipopolysaccharide/D-galactosamine (LPS/D-Gal) induced acute liver failure (ALF) in mice. Methods: Sixty-four mice were randomly divided into four groups, 16 in each group. ALF model of mice induced by intraperitoneal injection of LPS/D-Gal, the four groups were normal saline control group (a), LPS/D-Gal induction model group (b), LPS/D-Gal induction and PH797804 pretreatment group (c), PH797804 control group (d). The survival rate of mice was observed within 48 hours, and the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, the hepatic pathological changes were observed by HE staining tissue sections, and the expression levels of TNF-α and IL-6 were detected by Elisa. The high-throughput transcriptome sequencing was performed on the liver tissue of each group to explore the mechanism of action, and the sequencing results were verified by Real-time qPCR. Results: Compared with the ALF model group, the 48-hour survival rate of mice in group c after PH797804 treatment increased from 20% to 80%, the liver histopathological abnormalities of mice were significantly improved, the content of ALT and AST in serum were obviously lower than that in ALF model group(P＜0.01). And the content of proinflammatory cytokines such as TNF-α and IL-6 in serum were significantly lower than that in ALF model group(P＜0.01). In addition, RNA sequencing results suggested that the protective effect of PH797804 on LPS / D-Gal-induced ALF in mice is mainly related to inhibiting the inflammatory response. Real-time PCR verified the reliability of the sequencing results. Conclusion: PH797804 has protective effect on LPS / D-Gal-induced ALF in mice, and its mechanism may be related to inhibiting inflammatory response. |
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