Résumé
@#Objective To investigate the effects of salvianolic acids(SA) on improving cerebral ischemic damage through silencing information regulator protein 1 (SIRT1)/high-mobility group box 1 (HMGB1) signal pathway in rat. Methods 132 male general-grade healthy SD rats were randomly divided into four groups:sham operation group(Sham),ischemia model group(IS),SA group and inhibitor group(EX527). Focal cerebral ischemia was induced by occlusion of right MCA for 2 h. The neurological deficits were assessed by modified Neurological Severity Scores (mNSS) at 1,3,and 7 days after reperfusion. The concentrations of SIRT1,HMGB1 mRNA in peri-ischemic brain tissues were detected by RT-PCR at 1,3 and 7 days after reperfusion. SIRT1,HMGB1,P-53 and NF-κB protein expression were detected by Western blot. Serum P-53,NF-κB levels were measured by ELISA. The histomorphology in peri-ischemic brain tissues was observed by HE staining first day after reperfusion. The terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method was used to detect the neuronal apoptosis index. Results (1)Compared with IS and EX527 group,the mNSS score in SA group was significantly lower at 1 d,3 d and 7 d after reperfusion. (2)The expressions of HMGB1,P-53 and NF-κB in SA group were significantly lower than those in IS and EX527 group 7 d after reperfusion. The expression of HMGB1,P-53 and NF-κB protein in EX527 group was lower than that in IS group while it was significantly higher than the sham group 7 d after reperfusion. The expression of SIRT1 protein in SA group was significantly higher than that in IS and EX527 group,while the expression of SIRT1 protein in EX527 group was significantly higher than the sham group and IS group. (3)The expression of HMGB1 mRNA in SA group was significantly lower than that in sham group,IS group and EX527 group in the 7 d. The expression of HMGB1 mRNA in EX527 group was significantly higher than that in IS group and lower than that in sham group. The expression of SIRT1 mRNA in SA group was significantly higher than that in IS group,EX527 group and sham group. The expression of SIRT1 mRNA in EX527 group was significantly higher than that in sham operation and IS group. (4)The expressions of P-53 and NF-κB in peripheral blood of rats in SA group were significantly lower than those in IS group and EX527 group while the expression of P-53 and NF-κB protein in EX527 group was significantly lower than that in IS group and was higher than that in sham group at different time points. (5)The neuronal apoptosis index in SA group was significantly lower than that of IS group and EX527 group (P<0.05),while the neuronal apoptosis index of EX527group was significantly lower than that of IS group (P<0.05). Conclusion SA alleviate cerebral ischemc injury in rat by promoting SIRT1 transcription,inhibiting HMGB1 migration and expression,reducing the release of inflammatory factors P-53 and NF-κB in downstream pathways,and inhibiting neuronal apoptosis.