肌肽通过调节JNK和NF-kappaB通路抑制高糖诱导的心肌细胞凋亡(英文)

Carnosine Inhibits Cardiomyocyte Apoptosis via Modulation of the JNK and NF-kappaB Signaling Cascade in H9c2 Cells Exposed to High Glucose

高血糖症是糖尿病并发心血管疾病的重要危险因素.高血糖诱导产生的活性氧(ROS)能够引起糖尿病心肌病.我们的前期工作已经证实,肌肽对高糖环境下细胞凋亡具有保护作用,但其机制尚未明确.为研究肌肽对高糖诱导的大鼠心肌细胞凋亡的抑制作用及相关信号机制,以高糖诱导心肌细胞H9c2为模型,采用Brdu-ELISA法检测细胞增殖过程中DNA合成情况,流式细胞术检测细胞凋亡率,免疫印迹实验检测JNK/c-Jun、NF-κB的磷酸化水平,RT-PCR检测TNF-α的mRNA表达.实验结果显示,肌肽能够提高高糖损伤的H9c2细胞增殖能力,降低心肌细胞凋亡,抑制高糖激活的JNK、c-Jun和NF-κB磷酸化水平及TNFα的mRNA表达.上述结果表明,肌肽拮抗高糖诱导的心肌细胞凋亡机制与抑制p-JNK/p-c-Jun、p-NF-κB水平和TNF-α表达有关.

Hyperglycemia is an important risk factor for diabetes mellitus complicated with angiocardiopathy. Reactive oxygen species （ROS） induced by high glucose can cause diabetic cardiomyopathy. Previous works have showed that carnosine has a protective effect for apoptosis induced by high glucose, but the underlying mechanism remains unclear. To study the signaling mechanism of carnosine inhibiting high glucose induced-cardiomyocyte apoptosis, modeled on H9c2 induced by high glucose, DNA synthesis of cellular proliferation and cell apoptotic ratio were respectively assayed with Brdu-ELISA and flow cytometry, phosphorylation level of JNK/c-Jun and NF-κB were analyzed by Western blotting, the expression levels of TNF-α mRNA were further revealed by RT-PCR. The results show carnosine can improve cell proliferation ability of damaged H9c2, suppress high glucose-induced phosphorylation level of JNK/c-Jun and NF-κB, and the expression level of TNFα mRNA. These results indicate that the mechanism of carnosine against cardiomyocyte apoptosis induced by high glucose is attributed to the suppression of expression levels of p-JNK/p-c-Jun, p-NF-κB and TNF-α mRNA.