人参皂甙Rbl通过PKC途径抑制ET-1诱发的乳鼠心肌肥大

Ginsenosides-Rbl inhibits ET-1-induced cardiomyocyte hypertrophy via PKC pathway in neonatal rats

目的：探讨人参皂甙 Rb1（Gs-Rb1）是否可通过蛋白激酶 C （PKC）系统减轻内皮素-1（ET-1）诱导的乳鼠心肌细胞肥大。方法：将乳鼠心肌细胞随机分为空白对照组、Gs-Rb1组、ET-1组、Gs-Rb1＋ ET-1组、ET-1＋CHE 组（PKC 阻断剂白屈菜季氨碱）组和 Gs-Rb1＋ET-1＋CHE 组；干预96 h 后，测定心肌细胞表面积、总蛋白含量、PKC 活性、c-fos 和 p-c-jun 表达。结果：（1）Gs-Rb1＋ ET-1组心肌细胞表面积、心肌细胞总蛋白含量显著少于 ET-1组（P ＜0.05～＜0.001）；而与 Gs-Rb1＋ET-1＋CHE 组没有统计学意义（P ＝0.569）；（2）Gs-Rb1＋ET-1组 PKC 活性较 ET-1组显著下降[（9.3±0.6）pmol·min^－1·mg^－1比（14.1±0.9）pmol·min^－1·mg^－1]，但显著强于 Gs-Rb1＋ET-1＋CHE 组[（2.7±0.2）pmol·min^－1·mg^－1]，P 均＜0.001；（3）ET-1组 c-fos、p-c-jun基因和蛋白的表达显著高于空白对照组（P 均＜0.001）；与 ET-1组比较，Gs-Rb1＋ET-1组 c-fos [mRNA／蛋白：（0.53±0.05／0.39±0.02）比（0.43±0.03／0.31±0.03）]、p-c-jun [mRNA／蛋白：（0.64±0.04／0.44±0.02）比（0.33±0.05／0.37±0.03）]表达和 ET-1＋CHE 组 c-fos [mRNA／蛋白：0.41±0.05／0.31±0.02]、p-c-jun [mR-NA／蛋白：0.31±0.05／0.36±0.03]表达均显著下降（P ＜0.05或＜0.001），Gs-Rb1＋ET-1＋CHE 组 c-fos、p-c-jun 基因和蛋白的表达显著低于 Gs-Rb1＋ET-1组和 ET-1＋CHE 组（P ＜0.05或＜0.001）。结论：Gs-Rb1显著抑制 ET-1所致的心肌细胞肥大，PKC 系统是介导此生物学效应的途径之一。

Objective：To explore whether ginsenosides-Rb1 （Gs-Rb1）can relieve cardiomyocyte hypertrophy induced by endothelin-1 （ET-1）via protein kinase C （PKC）system.Methods：Cardiomyocytes of neonatal rat were random-ly divided into blank control group,Gs-Rb1 group,ET-1 group,Gs-Rb1＋ET-1 group,ET-1＋CHE （chelerythrine, PKC blocker）group and Gs-Rb1 ＋ET-1 ＋CHE group.After 96h intervention,cardiomyocyte surface area,total protein content,PKC activity,c-fos and p-c-jun expressions were measured.Results： （1）Cardiomyocyte surface area and total protein content in Gs-Rb1＋ET-1 group were significantly lower than those of ET-1 group （P 〈0.050〈0.001）,but not significant different with those of Gs-Rb1＋ET-1＋CHE group,P =0.569;（2）PKC activity in Gs-Rb1＋ET-1 group was significantly lower than that of ET-1 group [（9.3±0.6）pmol·min^-1 ·mg^-1 vs.（14.1± 0.9）pmol·min^-1 ·mg^-1 ],but significantly higher than that of Gs-Rb1＋ET-1＋CHE group [（2.7±0.2）pmol· min^-1 ·mg^-1 ],P 〈0.001 all;（3）Expressions of c-fos and p-c-jun gene and protein in ET-1 group were significant-ly higher than those of blank control group （P 〈0.001 all）;compared with ET-1 group,there were significant re-ductions in expressions of c-fos [mRNA/protein：（0.53±0.05/0.39±0.02）vs.（0.43±0.03/0.31±0.03）]and p-c-jun [mRNA/protein：（0.64±0.04/0.44±0.02）vs.（0.33±0.05/0.37±0.03）]in Gs-Rb1＋ET-1 group and ex-pressions of c-fos [mRNA/protein：0.41 ± 0.05/0.31 ± 0.02]and p-c-jun [mRNA/protein：0.31 ± 0.05/0.36 ±0.03]in ET-1＋CHE group （P 〈0.05 or 〈0.001）,expressions of c-fos and p-c-jun gene and protein in Gs-Rb1＋ET-1＋CHE group were significantly lower than those of Gs-Rb1＋ET-1 group and ET-1＋CHE group （P 〈0.05 or〈0.001）.Conclusion：Gs-Rb1 can significantly inhibit cardiomyocyte hypertrophy induced by ET-1 and PKC system is one of pathways mediating this biological effect.