黄嘌呤氧化酶和对氧磷酶1与非酒精性脂肪性肝病发生、发展的关系

Study on the relationship between xanthine oxidase paraoxonase-1 and occurrence and development of nonalcoholic fatty liver disease

目的观察黄嘌呤氧化酶(XOD)和对氧磷酶1(PON1)活力在非酒精性脂肪性肝病(NAFLD)发生及发展过程中的变化并探讨其与NAFLD严重程度的关系。方法采用高脂饮食(HFD)喂养大鼠建立NAFLD模型,32只雄性SD大鼠,随机均分4组:正常对照组、HFD组、HFD+α-硫辛酸(α-LA)40 mg/kg和20 mg/kg干预组。测量大鼠体重、肝重,常规HE染色观察肝脏病理形态学改变,检测血清和肝组织XOD和PON1活力、相关脂质指标和氧化应激指标。结果 HFD饲养12周可成功诱导大鼠NAFLD模型建立,表现为血脂紊乱、肝细胞脂质沉积及氧化应激。与正常对照组比较,HFD组大鼠血清XOD活力从第4周末明显升高,12周末达最高(P<0.01);PON1活力从4周末开始呈梯度降低趋势(P<0.01)。与HFD组比较,α-LA干预组能显著降低TG和升高的XOD,同时使下降的PON1有所恢复。肝组织的变化趋势与血清相同。结论 XOD和PON1活力在NAFLD形成的不同时期存在显著差异,提示其在该病发生发展过程中起了重要作用,对二者活力的检测有助于判断NAFLD严重程度。α-LA对NAFLD有一定的防治作用,作用机制可能与其抗氧化应激和抗脂质过氧化有关。

Objective To observe changes of xanthine oxidase （XOD）and paraoxonase-1 （PON1 ）in nonalcoholic fatty liver disease （NAFLD）in rats,and study the relevance of activity of XOD and PON1 with the severity of NAFLD. Methods A model of NAFLD in rats was established by intaking high fat diet （HFD）.Thirty-two rats were randomly assigned to normal group,NAFLD model group,NAFLD with different dosage ofα-LA （α-LA：20 or 40mg/kg）groups, 8 rats for each group.Body weight and liver weight of rats were measured.Histological changes were observed by HE staining.Xanthine oxidase （XOD）and paraoxon-1 （PON1 ）were detected in blood serum and liver tissue.Related lipid content and redox indicators were also determined.Results Rat model of NAFLD was induced successfully by HFD for 12 weeks,with obvious NAFLD-associated symptoms,namely blood lipid disorders,hepatic fat deposition and oxidative stress damage.XOD in serum increased significantly from the 4th week,remarkably higher than the normal group and reached the pinnacle at the 12th week （P 〈0.01 ）.In addition,a negative correlation between PON1 and XOD was observed.Compared with the model group,α-LA medication could obviously decrease TG and XOD activity,enhance PON1 activity.Similar results were also found in liver tissue.Conclusion There were significant differences of both XOD and PON1 activity in different periods of NAFLD,indicating their important role in the occurrence and development of NAFLD.Furthermore,the detection of XOD and PON1 activity might be noninvasive approaches for identifying the severity of NAFLD in clinical practice.Besides,α-LA showed a protective effect on NAFLD rats.The potential mechanism may be related to the inhibition of oxidative stress and anti-lipid peroxidation.