丙酮酸乙酯对D-氨基半乳糖诱导的急性肝损伤大鼠的保护作用

The protective effect of ethyl pyruvate on acute hepatic injury induced by D-galactosamine hydrochlorate in rats

目的观察丙酮酸乙酯(EP)对D-氨基半乳糖盐酸盐诱导的急性肝损伤模型大鼠的保护作用,并探讨其作用机制。方法制备D-氨基半乳糖盐酸盐诱导的急性肝损伤大鼠模型48只,并随机分成正常组、模型组、小剂量EP提前干预组、大剂量EP提前干预组、小剂量EP治疗组和大剂量EP治疗组。在造模后24h时取血,采用ELISA法检测TNF-α、IFN-γ、IL-10和IL-18水平;采用RT-PCR法检测肝组织HMGB1mRNA水平变化。结果与正常组比较,模型组大鼠血清TNF-α、IFN-γ、IL-10和IL-18水平均无明显变化(P>0.05),而肝组织HMGB1mRNA水平明显升高(P<0.01);与模型组比较,EP提前干预组和EP治疗组动物血清TNF-α、IFN-γ、IL-10和IL-18水平均无明显变化,而EP提前干预则显著降低了肝组织HMGB1mRNA水平(P<0.01),其中大剂量组最为显著(P<0.01);病理学检查显示,EP提前干预组大鼠肝组织学得到明显改善,尤其是在大剂量组,而且比EP治疗组更加显著。结论EP能有效保护D-氨基半乳糖盐酸盐诱导的大鼠急性肝损伤,保护效果与药物的干预剂量成正相关,并且提前干预的效果更明显。

Objective To observe the protective effect of ethyl pyruvate （EP） on acute hepatic injury induced by D-galactosamine hydrochlorate in ras. Methods The acute hepatic injury induced by D-galactosamine hydrochlorate were prepared in 48 male Wistar rats and the animals were divided at random into normal,model,early interference of low dose of EP,early interference of high dose of EP,low dose of EP treatment and high dose of EP treatment groups. 24 hours after modeling,the serum levels of TNF-α,IFN-γ,IL-10 and IL-18 were assayed by ELISA,the changes of high mobility group box 1 protein （HMGB1） mRNA in liver tissues were determined by RT-PCR,and the pathological changes of liver tissues were detected by HE staining. Results The levels of HMGB1 mRNA in liver tissues of model rats were significantly higher than normal group （P〈0.01）,while serum levels of TNF-α,IFN-γ,IL-10 and IL-18 in model group had no obvious changes （P〉0.05）. Compared with model group,the levels of serum TNF-α,IFN-γ,IL-10 and IL-18 had no obvious changes in EP early interference group or in EP treatment group,but the HMGB1 mRNA levels in liver tissues in EP early interference group were obviously decreased （P〈0.01）,especially in high-dose group,which was more obvious than in EP treatment group （P〈0.01）. The histopathological changes in the livers was most significantly improved in EP early interference,especially in high dose group. Conclusion Ethyl pyruvate could protect effectively the acute liver injury induced by D-galactosamine hydrochlorate in rats,and the protective effect is shown as a dose-and time-dependent manner.