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[白三烯C4合成酶同源物在刀豆蛋白A诱导的小鼠肝炎中的基因表达及环孢素A的调节作用]

[Gene expressions of LTC4 synthase homologs in Con A-induced mouse hepatitis and regulative effect of cyclosporine A].

作者信息

Qi Luo-yang, Ma Kui-fen, Lai Fang-fang

机构信息

Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 May;36(3):241-6. doi: 10.3785/j.issn.1008-9292.2007.03.006.

Abstract

OBJECTIVE

To explore the gene expressions of LTC4 synthase homologs in concanavalin A (Con A)-induced mouse hepatitis and regulation role of cyclosporine A (Cs A) treatment.

METHODS

Male Balb/c mouse liver injury model was developed by iv injection of Con A (20 mg/kg) and protected by Cs A pretreatment (150 mg/kg) before Con A administration. Blood samples were collected at indicated times after Con A treatment with or without Cs A pretreatment. Liver damage was assessed by serum transaminase ALT and AST measurement and histological evaluation. Meantime, three LTC4 synthase homolog gene expressions were determined by RT-PCR.

RESULTS

Serum ALT and AST upregulation were accompanied with histological damage at 2 h after Con A administration, and further aggravated at 8 h. mGST2 gene expression increased 1.7 fold at 2 h and 1.9 fold at 8 h, while the expression of LTC4 S and mGST3 changed little. Pretreatment with Cs A prevented mouse liver from injury by Con A and partly inhibited the mGST2 gene expression upregulation.

CONCLUSIONS

Administration of Con A in mouse lead to a significant increase of mGST2 gene expression without any significant effect on LTC4 S and mGST3 mRNA levels. Cs A pretreatment results in protection of liver damage, whereas fails to fully inhibit the increase of mGST2 gene expression.

摘要

目的

探讨白三烯C4合成酶同源物在刀豆蛋白A(Con A)诱导的小鼠肝炎中的基因表达以及环孢素A(Cs A)治疗的调节作用。

方法

通过静脉注射Con A(20 mg/kg)建立雄性Balb/c小鼠肝损伤模型,并在给予Con A前用Cs A预处理(150 mg/kg)进行保护。在Con A治疗后不同时间点,无论有无Cs A预处理,均采集血样。通过测定血清转氨酶ALT和AST以及组织学评估来评价肝损伤。同时,采用逆转录-聚合酶链反应(RT-PCR)检测三种白三烯C4合成酶同源基因的表达。

结果

Con A给药后2小时血清ALT和AST上调,并伴有组织学损伤,8小时时进一步加重。mGST2基因表达在2小时时增加1.7倍,8小时时增加1.9倍,而白三烯C4合成酶(LTC4 S)和mGST3的表达变化不大。Cs A预处理可预防Con A诱导的小鼠肝损伤,并部分抑制mGST2基因表达上调。

结论

给小鼠注射Con A可导致mGST2基因表达显著增加,而对白三烯C4合成酶和mGST3 mRNA水平无显著影响。Cs A预处理可保护肝脏免受损伤,但未能完全抑制mGST2基因表达的增加。

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