丙泊酚对非酒精性脂肪性肝病大鼠肝脏脂质堆积、肝损伤及氧化应激的调节作用

Regulatory effects of propofol on hepatic lipid accumulation,liveRinjury and oxidative stress in rats with non-alcoholic fatty liveRdisease

目的探讨丙泊酚对非酒精性脂肪性肝病(NAFLD)大鼠肝脏脂质堆积、肝损伤及氧化应激的调节作用。方法将40只SPF级SD大鼠随机分成对照组、模型组、丙泊酚低剂量组、丙泊酚中剂量组、丙泊酚高剂量组,每组8只。对照组大鼠喂食标准大鼠食物,模型组与丙泊酚低、中、高剂量组大鼠喂食高脂高糖食物;6周后,丙泊酚处理组分别喂食25 mg/kg、50 mg/kg、100 mg/kg丙泊酚,1次/d,连续4周。测量各组大鼠肝脏重量,计算肝指数;比较各组大鼠的血清脂质代谢指标水平(LDL、三酰甘油、总胆固醇、HDL)和氧化应激指标[超氧化物歧化酶(SOD)、丙二醛、乳酸脱氢酶(LDH)];采用HE染色和TUNEL染色观察各组大鼠的肝脏组织病理学变化和肝细胞凋亡情况,采用油红O染色观察大鼠肝细胞脂质分解情况,采用蛋白免疫印迹法检测大鼠肝组织中B细胞淋巴瘤-2(Bcl-2)基因、Bcl-2相关X蛋白(Bax)、乙酰辅酶A羧化酶(ACC)、肉毒碱棕榈酰基转移酶1(CPT-1)的相对表达量。结果模型组大鼠的肝脏重量、肝指数,血清LDL、三酰甘油、总胆固醇、丙二醛、LDH水平,肝脏组织细胞凋亡率及Bax与Bcl-2相对表达量的比值(Bax/Bcl-2)、ACC相对表达量均高于对照组(均P<0.05),而血清HDL、SOD水平及肝脏组织CPT-1相对表达量均低于对照组(均P<0.05)。丙泊酚中、高剂量组大鼠的肝脏重量、肝指数,血清LDL、三酰甘油、总胆固醇、丙二醛、LDH水平,肝脏组织细胞凋亡率及Bax/Bcl-2、ACC相对表达量均低于模型组(均P<0.05),血清HDL、SOD水平及肝脏组织CPT-1相对表达量均高于模型组,且除肝指数外,丙泊酚高剂量组大鼠上述指标均优于丙泊酚中剂量组(均P<0.05),而除Bax/Bcl-2及ACC相对表达量外,丙泊酚低剂量组大鼠的上述指标与模型组差异均无统计学意义(均P>0.05)。结论给予100 mg/kg的丙泊酚干预不仅能够降低NAFLD大鼠的肝脏重量及肝指数,调节NAFLD引起的脂质代谢紊乱、促进脂质分解,还可以缓解氧化应激及细胞凋亡造成的肝损伤,阻止NAFLD的进一步发展。

Objective To explore the regulatory effects of propofol on hepatic lipid accumulation,liveRinjury and oxidative stress in rats with non-alcoholic fatty liveRdisease(NAFLD).Methods Forty SPF-grade SD rats were randomly divided into control group,model group,low-dose propofol group,medium-dose propofol group and high-dose propofol group,with eight rats in each group.Rats in the control group were fed with standard rat food,and rats in the model,low-,medium-and high-dose propofol groups were fed with high-fat and high-sugaRfood;afteRsix weeks,the propofol treatment groups were fed with 25 mg/kg,50 mg/kg and 100 mg/kg propofol,respectively,once daily foRfouRconsecutive weeks.The liveRweight of rats in each group was measured and the liveRindex was calculated.Rats′serum levels of lipid metabolism indices(LDL,triacyglycerol,total cholesterol,HDL)and oxidative stress indices(superoxide dismutase[SOD],malondialdehyde,lactate dehydrogenase[LDH])were compared among groups.HE staining and TUNEL staining were used to observe the pathologic changes in liveRtissues and hepatocytes apoptosis of rats in each group,Oil red O staining to observe the lipidolysis of hepatocytes in rats,and Western blotting assay to detect the relative expression of B-cell lymphoma-2(Bcl-2)gene,Bcl-2 associated X protein(Bax),acetyl coenzyme A carboxylase(ACC),and carnitine palmitoyltransferase 1(CPT-1)in liveRtissues of rats.Results Rats in the model group yielded increases in liveRweight and liveRindex,higheRserum LDL,triacyglycerol,total cholesterol,malondialdehyde,and LDH levels,an elevated apoptosis rate in liveRtissues,a higheRratio of relative expression of Bax to relative expression of Bcl-2(Bax/Bcl-2),and increased relative expression of ACC,but loweRserum levels of HDL and SOD and decreased relative expression of CPT-1 in liveRtissues as compared with the control group(all P<0.05).Rats in the medium-and high-dose propofol groups exhibited declines in liveRweights and liveRindexes,loweRserum LDL,triacyglycerol,total cholesterol,malondialdehyde,and LDH levels,loweRapoptosis rates in liveRtissues,loweRBax/Bcl-2,and decreased relative expression of ACC in comparison with the model group(all P<0.05),togetheRwith serum HDL and SOD levels and relative expression of CPT-1 in liveRtissues higheRthan those in the model group;moreover,the high-dose propofol group was superioRto the medium-dose propofol group in the aforementioned indices of rats excluding the liveRindex(all P<0.05),whereas except foRBax/Bcl-2 and relative expression of ACC,the aforementioned indices of rats showed no statistically significant difference between the low-dose propofol group and the model group(all P>0.05).Conclusion Intervention with propofol(100 mg/kg)can not only reduce the liveRweight and liveRindex of NAFLD rats,regulate the disordeRof lipid metabolism caused by NAFLD and promote lipidolysis,but also alleviate oxidative stress and apoptosis-caused liveRinjury and prevent the furtheRdevelopment of NAFLD.