磷丙泊酚对大鼠肠缺血再灌注损伤的保护作用及机制研究

Protective effect and mechanism of fospropofol on intestinal ischemia-reperfusion injury in rats

目的 探究磷丙泊酚(FP)对大鼠肠缺血再灌注损伤(IRI)的保护作用及作用机制。方法 将SD雄性大鼠随机分为假手术组、模型组、丙泊酚组、磷丙泊酚组。所有大鼠均进行手术,使小肠缺血1 h,恢复供血再灌注2 h,建立大鼠肠IRI模型,假手术组进行假手术,模型组、丙泊酚组、磷丙泊酚组术前15 min分别尾静脉给予生理盐水、丙泊酚(20 mg·kg^(-1)·h^(-1))、磷丙泊酚钠(60 mg·kg^(-1)·h^(-1))。缺血再灌注结束后,检测肠组织湿质量/干质量(W/D)比值、丙二醛(MDA)含量、超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活性,并比较肠组织病理学结果及血红素氧合酶1(HO-1)和核因子-E2相关因子(Nrf2)蛋白表达情况。结果 假手术组、模型组、丙泊酚组、磷丙泊酚组的肠组织W/D比值分别为1.93±0.35、4.58±0.26、3.86±0.17和3.06±0.21;MDA含量分别为(26.64±3.84)、(78.24±3.93)、(65.87±4.12)和(41.35±2.35) nmol·mg^(-1);MPO活性分别为(1.19±0.28)、(5.92±0.58)、(4.51±0.33)和(2.86±0.31) U·g^(-1);SOD活性分别为(75.83±12.14)、(36.32±14.35)、(51.38±10.85)和(66.85±12.26) U·mg^(-1);4组大鼠肠组织Chiu评分分别为(1.93±0.35)、(4.58±0.26)、(3.86±0.17)和(3.06±0.21)分,肠组织HO-1蛋白表达量分别为0.26±0.04、0.58±0.05、0.71±0.04和0.82±0.06;Nrf2蛋白表达量分别为0.20±0.05、0.41±0.04、0.62±0.05和0.71±0.06。上述指标,模型组、丙泊酚组、磷丙泊酚组与假手术组比较,丙泊酚组、磷丙泊酚组与模型组比较,丙泊酚组与磷丙泊酚组比较,差异均有统计学意义(均P<0.05)。结论 磷丙泊酚对肠IRI具有保护作用,其保护机制与Nrf2-抗氧化反应元件(ARE)信号通路有关。

Objective To explore the protective effect and mechanism of fospropofol(FP)on intestinal ischemia-reperfusion injury(IRI)in rats.Methods SD male rats were randomly divided into sham operation group(sham group),model group,propofol group(P group),and fospropofol group(FP group).All rats were operated on to make the small intestine ischemia for 1 hour,and then perfused for 2 h after recovery.The rat intestinal IRI model was established,and the sham group pretended to be operated.Model group,P group and FP group were given normal saline,propofol(20 mg·kg^(-1)·h^(-1))and fospropofol(60 mg·kg^(-1)·h^(-1))15 min before operation,intravenous pump injection.After the IRI,the wet weight/dry weight(W/D)ratio malondialdehyde(MDA)content,superoxide dismutase(SOD)and leukocyte chemotactic factor(MPO)activities of the intestinal tissue were measured.And compared the intestinal histopathological results and the protein expression of heme oxygenase 1(HO-1)and nuclear factor erythroid-2-related factor 2(Nrf2).Results The W/D ratios of the sham group,model group,P group and FP group were 1.93±0.35,4.58±0.26,3.86±0.17 and 3.06±0.21,respectively;MDA content were(26.64±3.84),(78.24±3.93),(65.87±4.12),(41.35±2.35)nmol·mg^(-1),respectively;the MPO activity were(1.19±0.28),(5.92±0.58),(4.51±0.33),(2.86±0.31)U·g^(-1),respectively;SOD activity were(75.83±12.14),(36.32±14.35),(51.38±10.85),(66.85±12.26)U·mg^(-1),respectively;the Chiu scores of the four groups were 1.93±0.35,4.58±0.26,3.86±0.17,3.06±0.21,and the HO-1 protein expression levels of the four groups were 0.26±0.04,0.58±0.05,0.71±0.04 and0.82±0.06,respectively;Nrf2 protein expression levels were 0.20±0.05,0.41±0.04,0.62±0.05 and0.71±0.06,respectively.The above indexes were compared between model group,P group,PF group and sham group,between P group,PF group and model group,and between P group and PF group,the differences were statistically significant(all P<0.05).Conclusion Fospropofol has a protective effect on intestinal IRI,and its protective mechanism is related to the Nrf2-antioxidant response element(ARE)signaling pathway.