右美托咪定减轻酒精诱导的小鼠急性肝损伤
发布时间：2018-12-30 21:01
【摘要】：目的:探讨右美托咪定(DEX)对酒精诱导的小鼠急性肝损伤的作用及机制。方法:50只昆明小鼠随机分为5组(n=10):生理盐水对照(NS)组、酒精性肝损伤模型(E)组、DEX低剂量(10μg/kg)治疗(E+L)组、DEX中剂量(50μg/kg)治疗(E+M)组和DEX高剂量(100μg/kg)治疗(E+H)组。各组动物乙醇灌胃后6 h处死,采集血和肝组织标本。测定各组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平以及甘油三酯(TG)浓度;测定各组肝组织丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量及超氧化物歧化酶(SOD)活性;ELISA测定小鼠肝组织肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的浓度;Western blot检测肝组织细胞色素P4502E1(CYP2E1)和核因子κB(NF-κB)的表达;HE染色观察肝组织病理学改变并进行肝损伤评分。结果:与NS组比较,E组血清的AST、ALT水平及TG含量升高,与E组比较,E+M组和E+H组血清AST、ALT水平及TG含量降低;与NS组比较,E组肝组织MDA含量升高,GSH含量和SOD活性降低,与E组比较,E+M组和E+H组肝组织MDA含量降低,GSH含量及SOD活性升高;与NS组比较,E组肝组织TNF-α和IL-1β含量升高,与E组比较,E+M组和E+H组肝组织TNF-α和IL-1β含量降低;与NS组比较,E组肝组织CYP2E1和NF-κB表达升高,与E组比较,E+M组和E+H组肝组织CYP2E1和NF-κB表达降低;肝组织病理学检查可见,DEX中、高剂量可明显减轻肝细胞变性和坏死及炎性细胞浸润程度。结论:右美托咪定通过抗炎及抗氧化作用对急性酒精性损伤的肝脏具有一定的保护作用,其作用机制可能与抑制CYP2E1和NF-κB的表达有关。
[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 伪 (TNF- 伪) 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- 伪 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- 伪 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.
【作者单位】： 深圳市人民医院麻醉科 深圳市麻醉医学工程研究中心;深圳市罗湖医院集团湖贝社区健康服务中心;
【基金】：深圳市科技研发基金资助项目(No.JCYJ20160422142317026)
【分类号】：R614
，
本文编号：2396138
[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 伪 (TNF- 伪) 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- 伪 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- 伪 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.
【作者单位】： 深圳市人民医院麻醉科 深圳市麻醉医学工程研究中心;深圳市罗湖医院集团湖贝社区健康服务中心;
【基金】：深圳市科技研发基金资助项目(No.JCYJ20160422142317026)
【分类号】：R614
，
本文编号：2396138
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