番茄红素减轻H9C2心肌细胞缺氧/复氧致内质网应激的相关机制

目的 探讨番茄红素减轻H9C2心肌细胞缺氧/复氧(H/R)致内质网应激(ERS)的相关机制。方法 H9C2心肌细胞随机分为:①空白对照组、②番茄红素组、③H/R组、④番茄红素+H/R组、⑤4-苯基丁酸（4-phenyl butyric acid，4-PBA）+H/R组、⑥毒胡萝卜素内酯（thapsigargin，TG）组、⑦番茄红素+TG组。流式细胞术检测H9C2心肌细胞凋亡比例；Western blot检测葡萄糖调节蛋白(glucose-regulated proteins,GRP)78、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(C/EBP homologous protein,CHOP)、c-Jun氨基末端激酶(c-Jun-N-terminal protein kinase,JNK)、磷酸化JNK（p-JNK）及半胱氨酸天冬氨酸蛋白酶(Casepase)-12的表达。结果 与对照组相比，H/R组及TG组细胞的细胞凋亡比例、GRP78、CHOP、p-JNK和Caspase-12蛋白表达量明显增加（P<0.01）；与H/R组相比，细胞凋亡比例及上述蛋白表达在番茄红素+H/R组与4-PBA+H/R组明显下降（P<0.01）；与TG组相比，细胞凋亡比例及上述蛋白表达在番茄红素+TG组也明显下降（P<0.01）；而番茄红素+H/R组与4-PBA+H/R组相比差异不具有统计学意义。JNK蛋白总量表达无明显变化。结论 番茄红素通过抑制ERS致凋亡的相关信号通路CHOP、p-JNK和Caspase-12对H/R H9C2心肌细胞起到保护作用。

Mechanism of lycopene in alleviating endoplasmic reticulum stress induced by hypoxia/reoxygenation in H9C2 cardiomyocytes

AIM To explore the possible mechanism of lycopene in alleviating endoplasmic reticulum stress (ERS) induced by hypoxia/reoxygenation (H/R) in H9C2 cardiomyocytes. METHODS H9C2 cardiomyocytes were randomly divided into control group, lycopene group, H/R group, lycopene+H/R group, 4-phenyl butyric acid (4-PBA)+H/R group, thapsigargin (TG) group, and lycopene+TG group. The apoptosis ratio of H9C2 cardiomyocytes was detected and the expressions of protein of glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein kinase (JNK), phosphorylation of JNK (p-JNK) and caspase-12 were detected by Western blot. RESULTS The apoptosis ratio and the expressions of protein of GRP78, CHOP, JNK, p-JNK and caspase-12 increased markedly in H/R group and TG group in comparison with those in the control group (P<0.01). They decreased markedly in lycopene+H/R group and 4-PBA+H/R group compared with those in H/R group (P<0.01) and in lycopene+TG group compared with those in TG group (P<0.01). No statistically significant difference was found between lycopene+H/R group and 4-PBA+H/R group. No significant difference was found in the changes of the expression of protein of JNK. CONCLUSION Lycopene may exert its protective effect on H/R H9C2 cardiomyocytes through inhibiting the key signaling pathways of CHOP, p-JNK and caspase-12 to reduce ERS.