左卡尼汀调控钙调神经磷酸酶表达抑制过氧化氢诱导心肌细胞凋亡作用  

Anti-apoptotic effect of L-carnitine on H_2O_2-induced cardiomyocytes via inhibition of calcineurin overexpression

作　　者：贾桂枝[1] 王洪新[2] 李红[1] 王翠瑶[1] 戴红良[3] 

机构地区：[1]辽宁医学院生物化学与分子生物学教研室,辽宁锦州121001 [2]辽宁医学院药理学教研室,辽宁锦州121001 [3]辽宁医学院护理学院,辽宁锦州121001

出　　处：《中国药理学通报》2014年第3期129-132,共4页Chinese Pharmacological Bulletin

基　　金：辽宁省高等学校优秀人才支持计划(No 2008RC33)

摘　　要：目的研究钙调神经磷酸酶(CaN)是否参与左卡尼汀对过氧化氢(H2O2)诱导心肌细胞凋亡的抑制作用。方法将新生乳鼠心肌细胞体外培养进行实验,实验分为对照组、H2O2组、左卡尼汀+H2O2组、环孢素A(CsA)+H2O2组。对照组采用生理盐水;H2O2组加入200μmol·L-1H2O2孵育12 h;左卡尼汀+H2O2组、CsA+H2O2组分别给予1.2mmol·L-1左卡尼汀1 h或1μmol·L-1CsA 30 min预处理,再分别加入H2O2继续孵育12 h。通过流式细胞仪检测细胞凋亡率,蛋白质免疫印迹法检测cleaved caspase-3、Bcl-2和Bax等凋亡相关蛋白及CaN的表达。结果与对照组相比,H2O2组心肌细胞凋亡率、促凋亡蛋白cleaved caspase-3及Bax的表达均明显增加,而其抗凋亡蛋白Bcl-2的表达明显降低,左卡尼汀及CaN特异性抑制剂CsA可明显改善上述指标。而且,左卡尼汀还可抑制H2O2刺激下CaN的过表达。结论左卡尼汀可通过调控钙调神经磷酸酶表达抑制H2O2诱导的心肌细胞凋亡。Aim To explore whether ealeineurin （CaN） was involved in the inhibitory effect of L-earni- tine on H202-indueed eardiomyoeyte apoptosis. Meth- ods Neonatal rat eardiomyoeytes were randomly di- vided into control, H2O2, L-earnitine ＋ H2O2 and CsA ＋ H2O2 groups. Control group was treated with normal saline; H2O2 group was challenged by 200 ·mol · L 1 H2O2 for 12 h; L-earnitine ＋ H2O2 and CsA ＋ H2O2 groups were pretreated with 1.2 mmol · L 1 1 h or 1 ·mol · L 1 CsA 30 rain prior to 12 h H2O2 stimula- tion, respectively. Cell apoptotie rate was evaluated by flow eytometry, and expression of apoptosis relevant protein including cleaved easpase-3, Bel-2, Bax and CaN was determined by Western blot. Results Com- pared with control, H2O2 treatment induced a signifi- cant increase of eardiomyoeyte apoptosis. Meanwhile, expression of pro-apoptotie proteins cleaved easpase-3 and Bax increased, and anti-apoptotic protein Bcl-2 decreased. L-earnitine and CsA（ a specific inhibitor of CaN）, significantly attenuated above-mentioned abnor- malities. And also, L-earnitine greatly inhibited the overexpression of CaN induced by H2O2. Conclusion L-earnitine attenuates eardiomyoeyte apoptosis via modulating CaN expression.

关 键 词：左卡尼汀 H2O2 心肌细胞 凋亡 CaN caspase- 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]