益肝降脂方预处理对酒精性脂肪肝大鼠氧化应激的影响

Experimental searches for Yigan Jiangzhi Fang on peroxide damage

关键词:  益肝降脂方  酒精性脂肪肝  氧化应激  预处理  病理

Key words:  Yigan Jiangzhi Fang  alcoholic fatty liver disease  oxidative stress  pretreatment  pathology

摘要:

[目的] 观察不同浓度益肝降脂方(YGJZF)在不同时段干预酒精性脂肪肝(AFLD)大鼠的氧化应激效应,分析探讨YGJZF对AFLD大鼠的抗氧化作用及其可能机制.[方法] 97只SD大鼠随机分为模型组22只、中药YGJZF组75只,据干预时段和用药浓度不同,中药组分为中药3 w-Ⅰ及Ⅱ组、中药6 w-Ⅰ及Ⅱ组、中药9 w-Ⅰ及Ⅱ组共6组.采用梯度乙醇灌胃加高脂饲喂法造模.中药各组自第3、6、9周起予等效剂量[13.95g/(kg·ｄ)]和高剂量[27.9 g/(kg·d)]灌胃,模型组均予生理盐水15 mL/kg灌胃,至12周末.于第6、9、12周末观察大鼠血清8-异前列腺素F2α(8-iso-PGF2α)含量,肝匀浆丙二醛(MDA)含量、黄嘌呤氧化酮(XOD)活性及病理变化.[结果] 与各相应时段模型组比较:第6周末,中药3 w-Ⅱ组大鼠血清8-iso-PGF2α含量及肝匀浆MDA含量、XOD活性明显降低(P<0.05);第9周末的中药6 w组及第12周末的中药3 w、6 w、9 w各组大鼠血清8-iso-PGF2α含量、肝匀浆MDA含量、XOD活性均明显降低(P<0.05),且均以II组更明显;第12周末,中药组各指标降低顺序为中药3 w组 > 中药6 w组 > 中药9 w组;中药3 w-Ⅰ组及9 w-Ⅰ组8-iso-PGF2α、MDA含量均较中药6 w-Ⅰ组有统计学意义(P<0.05),中药3 w-Ⅱ、9 w-Ⅱ组8-iso-PGF2α含量均较中药6 w-Ⅱ组差异有统计学意义(P<0.05),中药Ⅱ组各指标均低于中药Ⅰ组,其中中药3 w组8-iso-PGF2α和MDA、XOD,中药6 w组8-iso-PGF2α和MDA,中药9 w组XOD均存在统计学差异(P<0.05);第6、9、12周末,中药各组HE病理示肝脏脂肪变均较模型组不同程度减轻,且以Ⅱ组更明显;第12周末,中药3 w组脂肪变轻于中药6 w组,中药6 w组稍轻于中药9 w组.[结论] 中药YGJZF不同时段干预均能降低乙醇诱导SD脂肪肝大鼠氧化应激损伤,且越早期干预抗损伤效应越突出,不同程度抑制了酒精肝大鼠的病理损伤,并呈现一定时间和浓度依赖性,为临床AFLD防护的用药与时机选择提供了实验依据.

Abstract:

[Objective] To explore intervention effect of oxidative stress effect for AFLD rats at different times, to analyze antioxygenation of YGJZF to AFLD rats and surgery its possible mechanisms. [Methods] The 97 SD rats were randomized into model group 22 and YGJZF group 75, which were divided into six groups. The model rats were induced by gradient ethanol gavage and high fat feeding method. Alcohol by gavage in half an hour, rats in YGJZF groups were given equivalent and high dose[13.95(g/kg·d)and 27.9(g/kg·d)]of YGJZF since the third, sixth and ninth week respectively, and in model groups normal saline(1.5 mL/kg), until the end of 12th week, at the end of third, sixth and ninth week, the serum values of ALT, AST, TC, TG, 8-iso-PGF2α, and hepatic tissue' change of MDA, XOD and pathological. [Results] Compared with corresponding model groups, at the end of the 6th week, in 3w-Ⅱ group the level of 8-iso-PGF2α, MDA and XOD reduced obviously(P<0.05). At the end of the 9th and 12th week, the level of 8-iso-PGF2α、MDA and XOD reduced obviously(P<0.05), particularly in II group. At the end of 12th week, the results in the 3 w group were the best, and in the 9 w group were the worst, the difference between 3w-I, 9w-I and 6w-I in TG, 8-iso-PGF2α, MDA was remarkable(P<0.05); each index in YGJZF-II group was lower in YGJZF-I group, especially the value of 8-iso-PGF2α in 3w group; 8-iso-PGF2α and MDA in 6w group; XOD in 9w group(P<0.05). At the end of the 6th, 9th and 12th week, compared with model groups, the degree of hepatic fatty change alleviated to some extent particularly in II group; and at the end of the 12th week, the change in 3 w group was beater than in 6w group, in the same between the 6w group and 9w group. [Conclusion] This article showed that YGJZF played a role in reducing SD rats' oxidative stress injury caused by alcohol in different periods of intervention, especially when the earlier intervention was done, and restrained pathological injure of AFLD rats presenting time and concentration dependence to some extent, which provided the experimental basis for the chooses of medication and time in the prevention and control of AFLD in clinic.