【摘要】：目的:探討右美托咪定(DEX)對酒精誘導的小鼠急性肝損傷的作用及機制。方法:50只昆明小鼠隨機分為5組(n=10):生理鹽水對照(NS)組、酒精性肝損傷模型(E)組、DEX低劑量(10μg/kg)治療(E+L)組、DEX中劑量(50μg/kg)治療(E+M)組和DEX高劑量(100μg/kg)治療(E+H)組。各組動物乙醇灌胃后6 h處死,采集血和肝組織標本。測定各組血清丙氨酸氨基轉移酶(ALT)、天冬氨酸氨基轉移酶(AST)水平以及甘油三酯(TG)濃度;測定各組肝組織丙二醛(MDA)、還原型谷胱甘肽(GSH)的含量及超氧化物歧化酶(SOD)活性;ELISA測定小鼠肝組織腫瘤壞死因子α(TNF-α)和白細胞介素1β(IL-1β)的濃度;Western blot檢測肝組織細胞色素P4502E1(CYP2E1)和核因子κB(NF-κB)的表達;HE染色觀察肝組織病理學改變并進行肝損傷評分。結果:與NS組比較,E組血清的AST、ALT水平及TG含量升高,與E組比較,E+M組和E+H組血清AST、ALT水平及TG含量降低;與NS組比較,E組肝組織MDA含量升高,GSH含量和SOD活性降低,與E組比較,E+M組和E+H組肝組織MDA含量降低,GSH含量及SOD活性升高;與NS組比較,E組肝組織TNF-α和IL-1β含量升高,與E組比較,E+M組和E+H組肝組織TNF-α和IL-1β含量降低;與NS組比較,E組肝組織CYP2E1和NF-κB表達升高,與E組比較,E+M組和E+H組肝組織CYP2E1和NF-κB表達降低;肝組織病理學檢查可見,DEX中、高劑量可明顯減輕肝細胞變性和壞死及炎性細胞浸潤程度。結論:右美托咪定通過抗炎及抗氧化作用對急性酒精性損傷的肝臟具有一定的保護作用,其作用機制可能與抑制CYP2E1和NF-κB的表達有關。
[Abstract]:Aim: to investigate the effect and mechanism of dexmetomidine (DEX) on acute liver injury induced by alcohol in mice. Methods: fifty Kunming mice were randomly divided into 5 groups (n = 10): normal saline control group (NS) group), alcoholic liver injury model group (E) group) and low dose (10 渭 g/kg) DEX treatment group (E L) group). The middle dose of DEX (50 渭 g/kg) was used to treat (E M) and the high dose of DEX (100 渭 g/kg) to treat (E H). The animals in each group were killed 6 hours after ethanol administration, and blood and liver tissue specimens were collected. The levels of serum alanine aminotransferase (ALT),) aspartate aminotransferase (AST) and triglyceride (TG) were measured. The content of malondialdehyde (MDA),) reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) were measured in liver tissue of each group, and the concentrations of tumor necrosis factor 偽 (TNF- 偽) and interleukin-1 尾 (IL-1 尾) in liver tissue of mice were measured by ELISA. The expression of cytochrome P4502E1 (CYP2E1) and nuclear factor-kappa B (NF- 魏 B) were detected by Western blot, the pathological changes of liver tissue were observed by HE staining and liver injury score was evaluated. Results: compared with NS group, the serum AST,ALT level and TG content in E group were higher than those in E group, and the serum AST,ALT level and TG content in E group and E H group were lower than those in E group. Compared with NS group, the content of MDA increased, the content of GSH and the activity of SOD decreased in group E, and the content of MDA, the content of GSH and the activity of SOD in liver tissue of group E and group E / H were lower than those in group E and E H, respectively. Compared with NS group, the contents of TNF- 偽 and IL-1 尾 in liver tissue in E group were higher than those in, E M group and E H group, and the contents of TNF- 偽 and IL-1 尾 in liver tissue in E group were lower than those in E group. Compared with NS group, the expression of CYP2E1 and NF- 魏 B in group E was higher than that in group E, and the expression of CYP2E1 and NF- 魏 B in group E was lower than that in group E and group E H. Histopathological examination showed that high dose of DEX could significantly reduce the degree of degeneration, necrosis and inflammatory cell infiltration of liver cells. Conclusion: dexmetidine has a protective effect on acute alcoholic liver injury through anti-inflammatory and anti-oxidation effects, and its mechanism may be related to the inhibition of the expression of CYP2E1 and NF- 魏 B.
【作者單位】： 深圳市人民醫(yī)院麻醉科 深圳市麻醉醫(yī)學工程研究中心;深圳市羅湖醫(yī)院集團湖貝社區(qū)健康服務中心;
【基金】：深圳市科技研發(fā)基金資助項目(No.JCYJ20160422142317026)
【分類號】：R614
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本文編號：2396138