Effect of RhoA inhibitor Y27632 on propofol-induced apoptosis of hippocampal neurons in neonatal rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effect of RhoA inhibitor Y27632 on the apoptosis of hippocampal neurons in neonatal rats induced by propofol.Methods Forty-eight neonatal Sprague Dawley (SD) rats at postnatal day 7 (P7) were randomly divided into normal saline group (NS group),RhoA inhibitor group (Y27632 group),Propofol group (Pro group) and RhoA inhibitor+Propofol group (Y27632+Pro group).NS group and Pro group were administrated intraperitoneally with 150μl normal saline.Twenty minutes later,Y27632 group and Y27632+Pro group were administrated intraperitoneally with 1 mg · kg-1 Y27632.And then the Pro group and Y27632+Pro group were exposed to propofol with first administration 30 mg · kg-1 and repeated administration 15 mg · kg-1for five times once an hour.Twenty-four hours after the final dose of the propofol,TUNEL was used to detect neuronal apoptosis of the hippocampal cells (n=6).And then,Western blot was used to test the proteins expression of cleaved caspase-3,calpain Ⅱ,Bcl-2 and Bax (n =6).Results (1) The number of TUNEL positive cells in the hippocampal CA 1 region were increased by 208.7％ in Pro group ((84.10± 12.03)/mm2) compared with that in NS group((27.24±6.29)/mm2) (P＜ 0.01),which it was significantly decreased by 68.1％ (P＜ 0.01) in Y27632 + Pro group ((50.02 ± 9.22) / mm2) compared with that in Pro group.Y27632 alone ((32.69±7.47)/mm2) did not increase the number of TUNEL positive cells.(2) Propofol increased the proteins expression of caspase-3 (P=0.0044),calpain Ⅱ (P=0.0012),Bax (P=0.0251),and decreased the proteins expression of Bcl-2 (P=0.0144).Pretreatment with Y27632 reversed propofol-induced the increase of cleaved caspase-3 (P=0.0027),calpain Ⅱ (P=0.0018) and Bax (P=0.0458),as well as the decrease of Bcl-2 (P=0.0184).Y27632 alone did not cause these protein change (P＞O.05).Conclusion RhoA inhibitor Y27632 can alleviate the hippocampus neuronal apoptosis of neonatal rat induced by propofol.