二乙酰胺三氮脒对大鼠非酒精性脂肪肝病的作用初步分析

Preliminary exploration of the effect of diminazene aceturate on nonalcoholic fatty liver disease in rats

旨在初步分析血管紧张素转换酶2(ACE2)的激活剂二乙酰胺三氮脒(DIZE)对高脂饮食诱导大鼠非酒精性脂肪肝病(NAFLD)的保护作用。利用高脂饮食诱导建立大鼠NAFLD模型,分为空白组、模型组、DIZE和阳性药物(洛伐他汀LOV)组,观察记录其生长状况。试验至第10周,剖检所有大鼠,采血测定血浆生化指标,取其肝脏观制作切片察病理变化。结果显示:1)第4周起模型组大鼠体重显著高于空白组(P<0.05),且血糖调节能力减弱,灌胃DIZE和LOV后大鼠增重得到控制,糖耐量有所恢复。2)与空白组相比,模型组大鼠血浆中甘油三酯(TG)、总胆固醇(TC)、总胆汁酸(TBA)含量和谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(AKP)和乳酸脱氢酶(LDH)活性极显著上升(P<0.01),游离脂肪酸(NEFA)含量显著下降(P<0.05)。灌胃DIZE和LOV后,TG、TC、AKP、LDH和TBA均极显著(P<0.01)下降,ALT和AST活性显著下降(P<0.05)。3)模型组大鼠肝组织中有大量脂肪滴,肝细胞发生脂肪变性,肝指数极显著高于空白组(P<0.01);灌胃DIZE后,肝指数减小,肝脏病理损伤有所缓解。综上,DIZE对高脂饮食诱导的NAFLD大鼠有保护作用,可显著降低大鼠血脂水平,改善血糖调节能力,缓解肝脏脂肪蓄积和脂肪变性,但其相关机制有待进一步研究,为DIZE成为新的NAFLD治疗药物的开发提供了理论依据。

The aim of the study was to investigate the protective effects of diminazene aceturate(DIZE),an activator of angiotensin-converting enzyme 2(ACE2),on high-fat diet induced nonalcoholic fatty liver disease(NAFLD)in rats.The rats were divided into control group,NAFLD model group,DIZE and lovastatin(LOV)groups,and the growth status was observed and recorded.At the 10 th week of the experiment,all rats were dissected.Blood samples were taken to determine plasma biochemical indicators,and liver tissue sections were prepared to observe pathological changes.The results showed that:1)From the 4 th week,the weight of the rats in the model group was significantly higher than the control group(P<0.05),whereas the blood glucose regulation ability was weakened.The weight gain of rats in the model group was controlled and the glucose tolerance was restored after intragastric administration of DIZE and LOV.2)Compared with the control group,the plasma levels of triglyceride(TG)、total cholesterol(TC)、total bile acid(TBA)and the activities of glutamic pyruvic transaminase(ALT)、glutamic oxalacetic transaminase(AST)、alkaline phosphatase(AKP)and Lactate dehydrogenase(LDH)in the model group increased extremely significantly(P<0.01),and the content of nonesterified fatty acid(NEFA)significantly decreased(P<0.05).After intragastric administration of DIZE and LOV,the plasma levels of TG、TC、AKP、LDH、TBA decreased significantly(P<0.01)and the ALT、AST activity significantly decreased(P<0.05).3)A large number of fat droplets existed in the liver tissue of the model group,the liver cells had fatty degeneration,and the liver index was extremely higher than that of the control group(P<0.01).After intragastric administration of DIZE,the liver index decreased and the liver pathological damage was relieved.In conclusion,DIZE has protective effect on NAFLD rats induced by high-fat diet,which can significantly reduce blood lipid levels,improve blood glucose regulation,and relieve liver fat accumulation and steatosis.However,its related mechanisms need to be further studied to provide theoretical basis for the development of DIZE as a new NAFLD treatment.