紫苏提取液对小鼠急性酒精中毒的作用及机制

Effects of aqueous extract of perilla leaves on acute alcohol toxication and its underlying mechanism in mice

目的:探讨紫苏提取液(PLE)对小鼠急性酒精中毒的作用及机制.方法:用食用白酒(56度)灌胃昆明种小鼠,建立急性酒精中毒动物模型.选取小鼠40只,随机分为4组,每组10只,分别为空白对照组、PLE低剂量组(20g/kg)、PLE高剂量组(40g/kg)、模型组.各实验组给予相应的药物30min后,除空白组外其余各组分别灌胃实验用酒0.15mL/10g,空白组灌以等量的生理盐水.分别观察紫苏提取液对小鼠醉酒潜伏时间及肝组织形态的影响.Real-time PCR检测小鼠肝组织中IL-6、iNOS、TNF-α、Bax基因mRNA的表达水平.结果:酒前灌PLE可降低醉酒小鼠数量、延迟小鼠发生醉酒的时间,其中高浓度组小鼠发生醉酒的潜伏时间与对照组相比有显著性差异(47.00±6.04vs11.56±12.11,P<0.05).正常对照组小鼠肝脏小叶、汇管区结构正常,肝细胞无明显变性、坏死,无明显炎细胞浸润.与模型组相比,PLE高剂量组与低剂量组肝细胞变性、坏死,炎细胞浸润均有明显改善.与模型组相比PLE可明显下调IL-6、iNOS、TNF-α mRNA的表达(0.251±0.073,0.455±0.096vs1.58±0.124;0.381±0.043,0.345±0.067vs2.088±0.088;0.584±0.061,0.270±0.027vs2.025±0.056,P<0.05或0.01),同时Bax mRNA的表达亦下降但无统计学差异.结论:紫苏提取液可显著地延长小鼠的醉酒潜伏时间、拮抗乙醇引起的肝脏损伤,此作用可能与其下调肝组织中IL-6等基因的表达有关.

AIM： To investigate the effects of aqueous extract of perilla leaves （PLE） on acute alcohol toxication and its underlying mechanism. METHODS： Alcohol was perfused to establish a mouse model of acute alcohol toxication. Forty Kunming mice （SPF）, were divided randomly into four groups： Blank, PLE of low dosage （20 g/kg）, PLE of high dosage （40 g/kg） and alcohol group. PLE were administered to the animals. Thirty minutes later, 0.015 mL/g ethanol was administered to each animal except the blank group which was given normal saline. The influence of PLE was observed. And pathologic changes of hepatic tissue were observed at microscopy and the mRNA expression of genes （IL-6, iNOS, TNF-α and Bax） in hepatic tissue were tested using real time RT-PCR. RESULTS： The quantity of drunken mice was obviously reduced, and the drunkenness time was delayed in PLE group especially in PLE of high dosage group（47.00 ± 6.04 vs 11.56 ± 12.11, P 〈 0.05）. The ethanol caused swelling of the liver cells, as well as neutrophilic infiltration and several ballooning degenerations of hepatocytes according to the microscopic examinations. However, the severe hepatic lesions induced by ethanol were considerably reduced following administration of different dosages of PLE. Compared with alcohol, PLE significantly down- regulated hepatic IL-6, iNOS, TNF-α mRNA transcription （0.251 ± 0.073, 0.455 ± 0.096 vs 1.58 ± 0.124; 0.381 ± 0.043, 0.345 ± 0.067 vs 2.088 ± 0.088; 0.584 ± 0.061, 0.270 ± 0.027 vs 2.025 ± 0.056, P 〈 0.05 or 0.01）, except Bax mRNA. CONCLUSION： PLE has the effect of anti-temulence, rivalrying the hepatic damage induced by ethanol, which might be associated with its roles in down-regulating IL-6, iNOS, TNF-α and Bax mRNA transcription in hepatic tissue.