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目的观察首剂治疗剂量环孢素A(CsA)、他克莫司(FK506)及雷帕霉素(Rapa)对独肾模型大鼠肝功能指标及肝脏组织病理的影响。方法将肾移植术后CsA、FK506和Rapa的首剂治疗剂量按公式换算为大鼠的用药剂量。40只SD大鼠随机分为正常组、对照组、CsA组、FK506组和Rapa组,每组8只,除正常组大鼠未行左肾切除术外,其余各组均构建独肾模型。造模后,CsA组给予CsA 25 mg/(kg.d),FK506组给予FK506 0.8mg/(kg.d),Rapa组给予Rapa 0.2 mg/(kg.d),而正常组和对照组则给予消毒饮用水1 mg/(kg.d)。持续给药8周后称取大鼠体重,检测血清白蛋白(Alb)、总蛋白(TP)、球蛋白(Glo)、胆红素(BIL)等肝功能指标,并观察各组大鼠肝脏组织的病理改变。结果 CsA组大鼠体重增长值、血清Alb均明显低于其他各组(P<0.05),TP低于正常组、对照组及Rapa组(P<0.05),BIL明显高于其他各组(P<0.05),FK506组TP明显低于正常组、对照组及Rapa组(P<0.05),Glo明显低于其他各组(P<0.05)。CsA组总胆红素(TBIL)、间接胆红素及直接胆红素均明显高于其他各组(P<0.05),FK506组TBIL低于正常组(P<0.05)。CsA组、FK506组、Rapa组较正常组和对照组均有不同程度的病理学改变,其中CsA组肝细胞广泛空泡样变,核固缩、崩解,局部可见脂肪滴,而FK506组及Rapa组除部分肝血窦窦周隙稍增大外,基本正常。结论治疗剂量CsA、FK506及Rapa对大鼠肝脏均有不同程度的影响;与CsA和FK506相比,Rapa引起大鼠体重增长值、BIL、Alb及Glo的改变较为轻微。
Objective To observe the effects of the first dose of CsA, FK506 and Rapa on the liver function and liver histopathology in the kidney of single kidney model rats. Methods The dose of the first dose of CsA, FK506 and Rapa after renal transplantation was converted into the dosage of rats according to the formula. Forty Sprague-Dawley rats were randomly divided into normal group, control group, CsA group, FK506 group and Rapa group, with 8 rats in each group. All the rats except the normal group were treated with left nephrectomy. CsA group received CsA 25 mg / (kg · d), FK506 group received FK506 0.8 mg / (kg · d), Rapa group received Rapa 0.2 mg / (kg · d), while those in normal group and control group Disinfect drinking water 1 mg / (kg.d). After 8 weeks of continuous administration, the body weight of rats was weighed and the indexes of liver function such as serum albumin (Alb), total protein (TP), globulin (Glo) and bilirubin (BIL) were measured. Tissue pathological changes. Results The body weight gain and serum Alb in CsA group were significantly lower than those in other groups (P <0.05). The TP level in CsA group was significantly lower than that in normal group, control group and Rapa group (P <0.05) <0.05). The TP in FK506 group was significantly lower than that in normal group, control group and Rapa group (P <0.05), and Glo was significantly lower than other groups (P <0.05). TBIL, indirect bilirubin and direct bilirubin in CsA group were significantly higher than those in other groups (P <0.05). TBIL in FK506 group was lower than that in normal group (P <0.05). CsA group, FK506 group, Rapa group than the normal group and the control group have varying degrees of pathological changes, including CsA group extensive vacuolar degeneration, nuclear pyknosis, disintegration, local visible fat droplets, and FK506 group and Rapa group except for part of sinusoidal sinusoidal space slightly increased, basically normal. Conclusion The therapeutic doses of CsA, FK506 and Rapa have different effects on the liver of rats. Compared with CsA and FK506, the changes of body weight gain, BIL, Alb and Glo in Rapa rats are slight.