茵栀黄口服液对溶血性黄疸小鼠模型的退黄作用及有效剂量和安全性研究

Research on the Effect of Yinzhihuang Oral Liquid on Antijaundice and Its Effective Dose and Safety in Mice with Hemolytic Jaundice

目的研究茵栀黄口服液对溶血性黄疸小鼠模型的退黄作用及有效剂量和安全性。方法将40只昆明小鼠随机分为造模组32只、正常组8只。造模组连续腹腔注射乙酰苯肼(APH)3 d后,将造模成功的昆明小鼠随机分为模型组和茵栀黄口服液的低、中、高剂量组,每组8只,模型组灌胃20 ml/(kg·d)的生理盐水;低、中、高剂量组分别灌胃5 ml/(kg·d)、10 ml/(kg·d)、20 ml/(kg·d)茵栀黄口服液(低、中剂量组分别于灌胃药物中分别加入15 ml/(kg·d)、10 ml/(kg·d)生理盐水,使3组灌胃总液体量均为20 ml/(kg·d));正常组腹腔注射生理盐水3 d后,灌胃20 ml/(kg·d)生理盐水。连续灌胃5d后取血,检测血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)、天门冬氨酸氨基酸转移酶(AST)、丙氨酸氨基酸转移酶(ALT)、碱性磷酸酶(ALP)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)和白球比(A/G),观察小鼠肝组织的病理切片。结果与正常组比较,造模组小鼠皮毛失去光泽、耳朵等处皮肤变黄、尿液黄,表明造模成功;模型组TBIL、DBIL、IBIL、GLB、A/G均明显升高(P<0.05),ALB、ALP降低(P<0.05),且以IBIL升高为主。与模型组比较,低剂量组TBIL降低(P>0.05),DBIL升高(P>0.05),IBIL降低(P<0.05);中、高剂量组TBIL、IBIL均降低(P<0.05),中、高剂量组的DBIL与模型组比较,差异无统计学意义;低、中、高剂量组的ALB、GLB、A/G与模型组比较,差异无统计学意义(P>0.05);各组间TP、AST、ALT、ALP差异无统计学意义(P>0.05);比较肝脏病理切片,与模型组比较,低、中、高剂量组肝组织损伤均有不同程度的改善;与低、中剂量组比较,高剂量模型组肝组织损伤加重。结论茵栀黄口服液对肝功能无明显影响;对肝组织损伤具有改善作用,高剂量对肝组织损伤的改善作用降低,其治疗溶血性黄疸昆明小鼠毒性剂量范围临界值在10 ml/(kg·d)与20 ml/(kg·d)之间,及退黄的有效剂量范围临界值在5 ml/(kg·d)与10 ml/(kg·d)之间。

Objective To study the antijaundice effect,effective dose and safety of Yinzhihuang oral solution in mice with hemolytic jaundice.Methods Forty Kunming mice were randomly divided into model group(32 mice)and normal group(8 mice),the mice were given APH by intrape ritoneal injection to inducehype rbilirubinemia.One course lasted for three days.The mices with successful established modes were divided into the model group and Yinzhihuang liquid low,middle and high dosage groups(8 mice).The model group were given 20 ml/(kg·d)saline solution by gavage.Yinzhihuang liquid low,middle and high dosage groups were respectively given 5,10 and 20 ml/(kg·d)Yinzhihuang liquid by gavage.One course lasted for five days,the normal group were given normal saline by intrape ritoneal injection and 20 ml/(kg·d)normal saline by gavage.The serum levels of TBIL,DBIL,IBIL,AST,ALT,ALP,TP,ALB,GLB and A/G were detected.Liver tissues of rats were taken for pathological examination.Results Compared with the normal group,the mice in the model group had withered fur,yellow skin and yellow urine,which indicated that the model was successful.Compared with the normal group,in the model group TBIL,DBIL,IBIL,GLB and A/G was evidently increased(P<0.05),ALB,ALP was evidently reduced(P<0.05),and indirect bilirubin were more increased,indicating that the hemolytic jaundice model was successfully constructed in mice.Comparing with those in the model group,in the low dosage group TBIL was reduced(P<0.05),DBIL was increased(P>0.05),and IBIL was reduced(P>0.05).In the middle and high dosage group TBIL was reduced(P<0.05).There was no difference in DBIL between the middle and high dosage groups and the model group(P>0.05).ALB,GLB and A/G in the low,middle and high dosage groups no difference compared with model group(P>0.05).There was no difference in TP,AST,ALT,ALP between the low,middle and high dosage groups and the model group(P>0.05).Compared with the model group,the liver injury in the low,middle and high dose groups was improved,and the liver injury in the high dosage groups was aggravated compared with that in the low and middle dose groups.Conclusion Yinzhihuang oral liquid had no obvious effect on liver function,and had ameliorative effect on liver tissue injury,but the ameliorative effect of high dose on liver tissue injury was decreased.The critical dose range for hemolytic jaundice in Kunming mice was between 10 ml/(kg.d)and 20 ml/(kg.d),the critical value of effective dose range is between 5 ml/(kg.d)and 10 ml/(kg.d).