| 宋银雪,王 军,高 烨,许 静,徐之超.糖皮质激素对小鼠急性肝衰竭的干预作用研究[J].,2021,(20):3818-3822 |
| 糖皮质激素对小鼠急性肝衰竭的干预作用研究 |
| The Effect of Glucocorticoids on Intervention of Acute Liver Failure in Mice |
| 投稿时间：2021-03-06 修订日期：2021-03-27 |
| DOI：10.13241/j.cnki.pmb.2021.20.004 |
| 中文关键词: 糖皮质激素 急性肝衰竭 SOX9 Hedgehog信号通路 |
| 英文关键词: Glucocorticoid Acute liver failure SOX9 Hedgehog signaling pathway |
| 基金项目:国家自然科学基金项目（81601674）；西安交通大学第一附属医院基金面上项目(2018MSZC-03) |
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| 中文摘要: |
| 摘要 目的：探讨糖皮质激素对小鼠急性肝衰竭（Acute liver failure, AHF）的干预作用。方法：通过腹腔注射D-GaIN/LPS构建AHF小鼠模型，并随机分为对照组、AHF模型组（AHF组）和糖皮质激素处理急性肝衰竭组（GCs + AHF组）。通过全自动生物化学分析仪检测小鼠血清中ALT、AST、TBA、TBIL、DBIL水平；采用ELISA试剂盒测定小鼠血清中IL-1β、TNF-α、IL-6水平；通过定量PCR检测mRNA表达水平；苏木精-伊红（H&E）染色检测肝组织病理学情况；免疫组织化学检测肝组织中SOX9表达水平；蛋白质印迹检测Hedgehog信号通路关键蛋白因子的表达水平。结果：与对照组相比，AHF组小鼠血清ALT、AST、TBA、TBIL、DBIL、MDA、TNF-α、IL-1β和IL-6水平显著升高，SOD、GSH和CAT活性水平显著降低（P＜0.01）；与AHF组相比，GCs+AHF组小鼠血清中ALT、AST、TBA、TBIL、DBIL、MDA、TNF-α、IL-1β和IL-6水平显著降低，SOD、GSH和CAT活性水平显著升高（P＜0.01）。H&E染色结果显示，对照组小鼠的肝脏切片显示正常的细胞结构，AHF组小鼠出现广泛的细胞坏死和炎性细胞浸润；与AHF组相比，GCs + AHF组小鼠中细胞坏死和炎性细胞浸润等病理变化显著减弱。免疫组织化学结果显示：与对照组相比，AHF小鼠肝脏中SOX9的表达水平显著升高（P＜0.01）；与AHF组相比，GCs+AHF组小鼠肝脏中SOX9的表达水平显著降低（P＜0.01）。Western blotting结果显示，与对照组相比，AHF组小鼠的Hedgehog通路关键蛋白因子Shh、Ptch-1和Gli-1蛋白表达水平显著升高（P<0.01）；与AHF组相比，GCs+AHF组的Shh、Ptch-1和Gli-1蛋白表达水平显著降低（P<0.01）。结论：GCs可有效改善AHF小鼠肝功能指标，降低炎性因子表达，提高急性肝衰竭小鼠抗氧化能力，并使Hedgehog通路关键蛋白因子表达恢复正常。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of glucocorticoid on the intervention of mice with acute liver failure (AHF). Methods: AHF mouse model was established by intraperitoneal injection of D-GaIN /LPS. The mice were randomly divided into control group, AHF model group and glucocorticoid treated acute liver failure group. The levels of ALT, AST, TBA, TBIL and DBIL in serum of mouse were detected by automatic biochemical analyzer, and the levels of IL-1β, TNF-α and IL-6 in serum were determined by ELISA kit The expression of SOX9 in liver tissue was detected by immunohistochemistry, and the expression of key protein factors in Hedgehog signaling pathway was detected by Western blotting. Results: Compared with those in control group, the serum levels of ALT, AST, TBA, TBIL, DBIL, MDA, TNF-α, IL-1β and IL-6 in AHF group were significantly increased, while the activities of SOD, GSH and CAT were significantly decreased(P<0.01). Compared with AHF group, the serum levels of ALT, AST, TBA, TBIL, DBIL, MDA, TNF-α, IL-1β and IL-6 in GCs+AHF group were significantly decreased, while the activities of SOD, GSH and CAT were significantly increased(P<0.01). The results of H&E staining showed that the liver sections of control group showed normal cell structure, and AHF group showed extensive cell necrosis and inflammatory cell infiltration; compared with AHF group, the pathological changes such as cell necrosis and inflammatory cell infiltration in GCs+AHF group were significantly reduced. The results of immunohistochemistry showed that compared with control group, the expression level of SOX9 in the liver of AHF group was significantly increased(P<0.01), while compared with AHF group, the expression level of SOX9 in the liver of GCs+AHF group was significantly decreased(P<0.01). Western blotting results showed that compared with control group, the protein expression levels of Shh, Ptch-1 and Gli-1 of Hedgehog pathway in AHF group were significantly increased(P<0.01), while compared with AHF group, the protein expression levels of Shh, Ptch-1 and Gli-1 in GCs+AHF group were significantly decreased (P<0.01). Conclusion: GCs can effectively improve the liver function of AHF mice, reduce the expression of inflammatory factors, improve the antioxidant capacity of AHF mice, and normalize the expression of key protein factors of hedgehog pathway. |
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