Shen Xin, Zhao Ge, Wang Rui, Liu Tingting, Liu Lin
Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2013 Jan;33(1):80-5.
To observe the effect of resveratrol and propofol, used either alone or in combination, on hepatocyte apoptosis in rats with hepatic ischemia-reperfusion injury (HIRI).
A total of 144 male SD rats were randomized into 8 equal groups, including a sham-operated group and 7 HIRI (established using Pringle method) groups with pretreatments with normal saline, Tween80, propofol (10 or 20 mg·kg(-1)·h(-1)), or resveratrol (10 or 20 mg/kg), or both propofol and resveratrol 10 min before hepatic portal vein occlusion. At 1, 3 and 6 h after the reperfusion, 6 rats from each group were sacrificed for histopathological examination of the liver tissue, detection of hepatocyte apoptosis using TUNEL assay, and measurement of Bcl-2, Bax and caspase-3 protein expressions using immunohistochemistry.
Compared with normal saline and Tween80, propofol and resveratrol at different doses used alone or in combination all significantly alleviated the hepatic pathologies, lowered the apoptosis index (P<0.05), increased Bcl-2 expression (P<0.05), and reduced Bax and caspase-3 expressions in the liver tissues following HIRI (P<0.05). Compared with low doses of propofol and resveratrol used alone, their combination showed more obvious protective effects against hepatocyte apoptosis (P<0.05), but at higher doses, propofol and resveratrol either alone or in combination produced similar effects.
Propofol and resveratrol can suppress HIRI-induced hepatocyte apoptosis by up-regulating Bcl-2 and down-regulating Bax and caspase-3 expressions, and their combined use can reduce the effective doses of the drugs.
观察白藜芦醇和丙泊酚单独及联合应用对肝缺血再灌注损伤(HIRI)大鼠肝细胞凋亡的影响。
将144只雄性SD大鼠随机分为8组,每组18只,包括假手术组和7个HIRI组(采用Pringle法建立)。HIRI组于肝门静脉阻断前10 min分别给予生理盐水、吐温80、丙泊酚(10或20 mg·kg⁻¹·h⁻¹)、白藜芦醇(10或20 mg/kg)预处理,或丙泊酚与白藜芦醇联合预处理。再灌注后1、3和6 h,每组处死6只大鼠,取肝组织进行病理组织学检查,采用TUNEL法检测肝细胞凋亡,免疫组织化学法检测Bcl-2、Bax和caspase-3蛋白表达。
与生理盐水和吐温80组相比,不同剂量丙泊酚和白藜芦醇单独及联合应用均能显著减轻肝组织病理损伤,降低凋亡指数(P<0.05),增加Bcl-2表达(P<0.05),降低HIRI后肝组织中Bax和caspase-3表达(P<0.05)。与单独使用低剂量丙泊酚和白藜芦醇相比,二者联合应用对肝细胞凋亡的保护作用更明显(P<0.05),但高剂量时,丙泊酚和白藜芦醇单独及联合应用效果相似。
丙泊酚和白藜芦醇可通过上调Bcl-2表达、下调Bax和caspase-3表达抑制HIRI诱导的肝细胞凋亡,二者联合应用可降低药物有效剂量。