Protective effect of etomidate on carbon tetrachloride-induced liver injury in rats

LI Wen; LI Yu-juan; CHEN Lu; LI Shuang-qian; LIU Jun-hui; HAN Li-li

doi:10.11659/jjssx.09E022055

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Protective effect of etomidate on carbon tetrachloride-induced liver injury in rats

Basic Research | 更新时间：2023-11-24

- Protective effect of etomidate on carbon tetrachloride-induced liver injury in rats
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 11, Pages: 984-989(2023)
- 作者机构：
  
  河北北方学院附属第一医院创伤急救外科，河北张家口 075000
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.09E022055
  CLC： R575.3
- Published：25 November 2023，
  
  Received：09 September 2022，
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李雯,李玉娟,陈璐等.依托咪酯对四氯化碳诱导的大鼠肝损伤的保护作用[J].局解手术学杂志,2023,32(11):984-989.

LI Wen,LI Yu-juan,CHEN Lu,et al.Protective effect of etomidate on carbon tetrachloride-induced liver injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(11):984-989.
李雯,李玉娟,陈璐等.依托咪酯对四氯化碳诱导的大鼠肝损伤的保护作用[J].局解手术学杂志,2023,32(11):984-989. DOI： 10.11659/jjssx.09E022055.

LI Wen,LI Yu-juan,CHEN Lu,et al.Protective effect of etomidate on carbon tetrachloride-induced liver injury in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(11):984-989. DOI： 10.11659/jjssx.09E022055.

摘要

目的

研究依托咪酯对四氯化碳（CCl

）诱导的大鼠急性肝损伤的保护作用及相关机制。

方法

将48只SPF级Wistar大鼠随机分为对照组、模型组、依托咪酯0.5 mg/kg组、依托咪酯1 mg/kg组、依托咪酯2 mg/kg组、水飞蓟素（SIL）组（200 mg/kg，阳性对照），每组6只。对照组和模型组静脉注射生理盐水0.2 mL，依托咪酯给药组分别静脉注射0.5 mg/kg、1 mg/kg、2 mg/kg依托咪酯0.2 mL，SIL组静脉注射200 mg/kg SIL 0.2 mL，每天1次，连续给药14 d，然后模型组、依托咪酯给药组和SIL组腹腔注射0.2% CCl

（10 mL/kg），对照组腹腔注射等量橄榄油，24 h后处死大鼠。测定血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平；HE染色评估肝组织病理损伤；ELISA检测肝组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平；检测超氧化物歧化酶（SOD）和丙二醛（MDA）水平；TUNEL染色评估肝组织中细胞凋亡情况；免疫组化检测大鼠肝组织中NF-κB p65阳性表达；Western blot检测相关蛋白的表达。

结果

与对照组相比，模型组大鼠血清ALT和AST水平明显升高，肝组织病理损伤明显，TNF-α、IL-6、MDA水平显著升高，SOD水平显著降低，肝组织细胞凋亡数量明显增加，Bax/Bcl-2、cleaved caspase-3/caspase-3及p-NF-κB p65/NF-κB p65明显升高，差异均有统计学意义（

0.05）。与模型组相比，依托咪酯1 mg/kg组、依托咪酯2 mg/kg组、SIL组肝组织病理损伤明显改善，炎症因子释放、氧化应激和肝组织细胞凋亡得到抑制，p-NF-κB p65/NF-κB p65降低。

结论

依托咪酯对CCl

诱导的大鼠急性肝损伤具有较好的缓解作用，其机制可能与抑制NF-κB通路有关。

Abstract

Objective

To investigate the protective effect and related mechanism of etomidate on carbon tetrachloride （CCl

）-induced acute liver injury in rats.

Methods

A total of 48 SPF grade Wistar rats were randomly divided into the control group， the model group， the etomidate 0.5 mg/kg group， the etomidate 1 mg/kg group， the etomidate 2 mg/kg group and the silymarin （SIL） group （200 mg/kg， as positive control）， with 6 rats in each group. The control group and the model group received intravenous injection of 0.2 mL of normal saline， the etomidate groups received intravenous injection of 0.5 mg/kg， 1 mg/kg， and 2 mg/kg of etomidate 0.2 mL， and the SIL group received intravenous injection of 200 mg/kg of SIL 0.2 mL， once a day for 14 consecutive days. Then， the model group， the etomidate groups， and the SIL group received intraperitoneal injection of 0.2% CCl

（10 mL/kg）， and the control group received intraperitoneal injection of an equal amount of olive oil. After 24 hours， the rats were killed. The serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were determined. HE staining was used to evaluate the pathological damage of liver tissue. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in liver tissue were detected by ELISA. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected. TUNEL staining was used to evaluate apoptosis in liver tissue. The positive expression of NF-κB p65 in rat liver tissue was detected by immunohistochemistry. The expression of related proteins was detected by Western blot.

Results

Compared with the control group， the levels of serum ALT and AST in the model group were significantly increased， the pathological damage of liver tissue was obvious， the levels of TNF-α and IL-6， and MDA levels were significantly increased， the SOD level was significantly decreased， the number of liver tissue apoptosis was significantly increased， the Bax/Bcl-2， cleaved caspase-3/caspase-3， and p-NF-κB p65/NF-κB p65 were significantly increased， with statistically significant differences （

0.05）. Compared with the model group， the pathological damages of liver tissue in the etomidate 1 mg/kg group， the etomidate 2 mg/kg group and the SIL group was obviously improved， the release of inflammatory factors， oxidative stress， liver tissue apoptosis were inhibited， and the p-NF-κB p65/NF-κB p65 was reduced.

Conclusion

Etomidate has a good alleviating effect on CCl

-induced acute liver injury in rats， and its mechanism may be related to the inhibition of NF-κB pathway.

关键词

依托咪酯四氯化碳肝损伤白细胞介素-6丙二醛NF-κB p65

Keywords

etomidatecarbon tetrachlorideliver injuryinterleukin-6malondialdehydeNF-κB p65

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