卡维地洛对大鼠心肌TNF-α、TNF-αR1表达的影响  

The Effects of Carvedilol on Gene Expression of TNF-α、TNF-αR1 in Rats Cardiomyocyte

作　　者：沈玉芹[1] 吕立夏[2] 邓兵[3] 戚秀卿[3] 邓南伟[3] 徐文渊[3] 

机构地区：[1]同济大学附属同济医院急诊科,上海200065 [2]同济大学医学院生化教研室,上海200092 [3]同济大学附属同济医院心内科,上海200065

出　　处：《同济大学学报（医学版）》2004年第1期3-6,共4页Journal of Tongji University(Medical Science)

摘　　要：目的研究卡维地洛对大鼠心肌凋亡相关基因TNF-α、TNF-αR1表达的影响。方法SD大鼠随机分三组:对照组,阿霉素组,阿霉素+卡维地洛组;阿霉素腹腔注射(ADR 20 mg/kg)制备心肌毒性动物模型;卡维地洛组在注射阿霉素之后立即腹腔注射卡维地洛(Carv2 mg/kg);等量生理盐水用于对照组。于用药后第1、3、5、10、15天采用逆转录聚合酶链反应检测TNF-α,TNF-αR1在心肌细胞中的表达,HE染色检测心肌组织病理改变情况。结果GAPDH为内标,第1、3、5、10天阿霉素组TNF-α表达逐渐增强,TNF-αR1表达逐渐增强;阿霉素+卡维地洛组中TNF-α及TNF-αR1表达均逐渐增强;阿霉素+卡维地洛组与阿霉素组比较:TNF-α及TNF-αR1表达两组比较差异无显著性。HE染色结果:阿霉素组与卡维地洛组比较差异无显著性。结论(1)阿霉素的心肌毒性作用可增强心肌细胞凋亡相关基因TNF-α及TNF-αR1的表达;(2)卡维地洛对凋亡相关基因TNF-α及TNF-αR1的表达无影响;揭示卡维地洛对阿霉素心肌毒性的保护作用不能通过调节TNF-α、TNF-αR1的表达而实现。Objective To study the effect of Carvedilol on gene expression of TNF-α,TNF-αR1 in cardiomyte in rats. Methods SD rats were divided into three groups: control group, Adriamycin group, Adriamycin + Carvedilol group. The models of myocardium toxicity were prepared with intraperitoneal injection of Adriamycin (20 mg/kg ). Carvedilol was applied intraperitoneally followed Adriamycin administration with a dose of (2 mg/kg). The equivalent volume of normal saline was used in control group. The heart tissues were obtained at the 1,3,5,10, and 15 days after drug administration. The reverse transcription polymerase chain reaction was perfomed to assess the expression alternation of TNF-α and TNF-αR1 at different time course in mRNA level and hematoxylin staining was used to study its pathologic changes. Results (1) Normalized by GAPDH, the mRNA expression level of TNF-α showed a gradient increase tendency and TNF-αR1 also gave a gradient increase tendency in adriamycin group. In Adriamycin + Carvedilol group, the expression of TNFα and TNFα-R1 were also increased. Comparing with Adriamycin group, there was no significant difference about the expression of TNFα and TNFα-R1 between two groups(ADR and ADR+ CARV). (2) There was no significant difference between two groups (ADR and ADR + CARV) in pathologic findings. Conclusion (1) The toxicity of adriamycin can increase the gene expression of TNF-α and TNF-αR1; (2) No effect was found about Carvedilol on the expression of TNF-α and TNF-αR1. These data may provide useful clues to elucidate the fact that the protective mechanism of carvedilolis is not related to TNF-α and TNF-αR1 regulation.

关 键 词：卡维地洛 阿霉素 TNF-Α TNF-αR1 基因表达 大鼠 

分 类 号：Q753[生物学—分子生物学]