Effects of Radix Salvia Miltiorrhiza on expression of activating transcription factor-6α during the periods of hepatic ischemia-reperfusion in rats

Objective To investigate the expression of activating transcription factor-6α (ATF-6α) and cysteinylasparate specific proteinase-12 (Caspase-12) during the periods of hepatic ischemia-reperfusion iujury and the effect of radix Salvia mihiorrhiae (RSM).Methods A total of 80 Wistar rats were randomly divided into 4 groups:normal group (group A),sham-operated group (group B),ischemia-reperfusion group (group C) and RSM-pretreated group (group D).The model of hepatic ischemia-reperfusion injury was established by occlusion of hepatic pedicle.The expression levels of ATF-6α and Caspase-12 were detected by using Western blotting and immunohistochemistry at 45 min after ischemia and 0,3,12,24,72 h after reperfusion.Results There was no significant difference between group A and group B (P＞0.05).In groupC [0h (346.46±103.89),3 h (1190.70±134.88),12h (5456.18± 288.46),24 h (1772.60 ± 139.46),72 h (235.69 ± 68.15)],the expression of ATF-6α was higher than in group A (9.57±1.26) and groupB [0h (9.90±3.73),3 h (9.69±3.52),12 h (9.50± 2.31),24h (9.44 ±1.73),72 h (9.32 ±2.71)] (P＜0.01).In group C [0h (654.13 ±102.12),3 h (3004.09 ±505.77),12 h (6896.13 ±841.14),24 h (2364.03 ±276.68),72 h (674.96 ± 153.92)],the expression of Caspase-12 was higher than in group A (127.97 ±4.33) and group B [0 h (154.58 ±44.20),3 h (130.58 ±38.40),12 h (144.62 ±36.24),24 h (138.37 ±24.66),72 h (147.87 ±33.10)] (P ＜0.01).In group D,the expression levels of ATF-6α and Caspase-12 around the central veins and portal area were higher than in group A and group B (P ＜0.01),but lower than in group C (P ＜ 0.01).Conclusion The protective effect of RSM-pretreatment may regulate hepatocyte endoplasmic reticulum stress steady state and reduce the apoptosis during the periods of hepatic ischemia/reperfusion by maintaining the proper expression of ATF-6α and down-regulating the over-expression of Caspase-12 in rats. Key words: Radix salvia miltiorrhiza;  Liver ischemia;  Reperfusion injury;  Endoplasmic reticulum stress ;  Activating transcription factor-6α ;  Caspase-12