应用顺铂联合长春瑞滨后常规二维超声、ARFI以及病理对照综合评价对家兔肝损害的实验研究

Experimental study of rabbit liver function impairment evaluated by two-dimensional ultrasound and acoustic radiation force impulse imaging combining with pathology after administration of cisplatin and vinorelbine

目的应用化疗药顺铂及长春瑞滨后观察兔肝脏的常规超声表现、声辐射力脉冲成像(ARFI)测定值、实验室检测及病理改变,并对比研究用药后肝脏的病理损害与生化检验及超声所见的相互关系,重点观察肝脂肪变性的情况。方法健康雄性新西兰大耳白兔30只,应用简单随机法分为对照组(A组)、顺铂+长春瑞滨组(B组)及顺铂+长春瑞滨+高脂饲料(C组),每组10只。用药前测定兔肝功能及血脂,对兔肝行常规超声及声辐射力脉冲成像检查,应用6个周期化疗药后再次行上述检查,比较用药前后的肝功能、血脂、常规超声表现及ARFI测定值,最后行兔肝病理检查。结果A组用药前后丙氨酸氨基转移酶和天冬氨酸氨基转移酶差异无统计学意义,B组和C组用药后丙氨酸氨基转移酶和天冬氨酸氨基转移酶均较用药前升高(P值均<0.05),C组高于B组(F=1204.517、5695.501,P值均<0.001)。A组和B组用药前后总胆固醇和甘油三酯差异无统计学意义,C组用药后总胆固醇和甘油三酯均较用药前升高(t=441.536、10.506,P值均<0.05),且均高于A组和B组(F=122890.902、75.943,P值均<0.001)。A组用药后超声未见异常;B组应用化疗药后肝脏常规超声显示肝包膜稍增厚,肝实质回声不同程度增强,回声不均匀,胆管壁及门脉管壁回声增强;C组肝体积稍大,内部回声情况同B组,还可见肝实质回声稍致密增强,类似轻度脂肪肝的表现。A组用药前后ARFI测定值差异无统计学意义,B组和C组用药后ARFI测定值均较用药前增加(t=18.30、23.92,P值均<0.001),C组ARFI测定值高于B组(F=159.103,P<0.001)。A组用药前后无明显异常,B组可见肝细胞水肿,轻微散在脂肪变性,汇管区、小血管壁及小胆管壁炎细胞浸润、少许淤血及淤胆,点状坏死及少许纤维化等。C组除了B组病理损害外,还显示体积稍大,脂肪变性明显加重,还可见少许再生结节。结论单纯应用化疗药可引起不同程度的肝损害,但不会引起兔肝明显的脂肪肝病理改变,临床上出现的所谓"化疗性脂肪肝"主要是由过量高脂营养物质引起,高血脂易引起肝功能异常或加重肝功能损害。ARFI对化疗药物性肝损害评估有一定价值。

Objective To observe the ultrasonic characteristics,the measured value of acoustic radiation force impulse imaging(ARFI),the laboratory test and pathological changes of rabbit liver caused by cisplatin and vinorelbine,and study the relationship of the findings with the degree of liver fatty impairment.Methods 30 male New Zealand rabbits were randomly divided into three groups:control group(group A),cisplatin+vinorelbine group(group B)and cisplatin+vinorelbine+fat-diet group(group C).The liver function,blood lipid,conventional ultrasound and ARFI of the rabbit livers were detected before and after the treatment.After six cycles of drug(diet)administration,the above examinations were performed again.The data of laboratory test,conventional ultrasound and ARFI obtained before and after the treatment were compared.Finally,the rabbit liver pathology was detected.Results There was no statistically significant difference in aspartate aminotransferase and alanine aminotransferase in group A before and after treatment.Aspartate aminotransferase and alanine aminotransferase were increased in group B and group C after treatment(all P<0.05),and the values of group C were higher than those of group B(F=1204.517,5695.501,both P<0.001).Total cholesterol and triglyceride in group A and group B showed no statistically significant difference before and after treatment.Total cholesterol and triglyceride in group C were increased after treatment(t=441.536,10.506,both P<0.05),and the values were higher than those of group A and group B(F=122890.902,75.943,both P<0.001).There were no abnormal ultrasound findings in group A after treatment.Conventional ultrasound in group B after treatment showed thickening of liver capsule,varying degrees of increase and heterogeneous ehoes of parenchyma.The echoes of bile duct wall and portal vein wall were enhanced.In group C there was a little increase in hepatic volume and similar internal echoes with group B after treatment,and also there were enhanced and tense echoes of liver parenchyma,mimicking the sonogram of mild fatty liver.There was no statistically significant difference in ARFI before and after treatment in group A.ARFI in group B and group C were increased after treatment(t=18.30,23.92,both P<0.05),the value of group C was higher than that of group B(F=159.103,P<0.001).There were no abnormal findings in group A before and after treatment.In group B after treatment,there were hepatic hydropsy,mild sporadic fatty degeneration,inflammatory cell infiltration in portal area,in the walls of portal vein and bile duct,there were also some congestion and cholestasis,some spotty necrosis and fibroplasia.In group C after treatment,there were also obvious fatty degeneration and some regenerative nodules besides the findings in group B.Conclusions Application of chemotherapeutants can cause different levels of pathological changes,but unlikely cause marked rabbit fatty liver,the so-called clinically chemotherapeutant-induced fatty liver probably results from the over intake of nutritious food.ARFI has some value to evaluate the drug-induced liver damage.