目的 研究经大鼠溃疡皮肤反复给予含汞中药制剂引起的肾功能指标改变与肾脏病理形态的关系,为临床监测含汞制剂的安全性及明确诊断肾脏损害阶段提供依据.方法 将80只SD大鼠随机分8组:皮肤破损组,溃疡模型组,基质组(凡士林)及5个中药剂量A、B、C、D、E组(1.219、0.609、0.305、0.152、0.076 g/kg).连续给药14 d,采用酶联免疫法检测大鼠尿视黄醇结合蛋白(RBP),脲酶法检测血清尿素氮(BUN),除蛋白法检测血肌酐(SCr)；通过称量大鼠空腹体重及脏器湿重,计算肾脏系数；福尔马林溶液固定肾脏,HE染色观察肾组织形态.结果 与溃疡模型组比较,各组BUN及SCr未见异常；中药A、B、C、D组RBP水平均明显升高(P＜0.01)；各中药组肾脏系数均不同程度升高.肾组织形态观察,可见大面积创伤、细菌感染及炎症等病理因素可以造成溃疡模型大鼠肾脏病变,以肾间质出血及炎细胞浸润为主,而这种病理损害在各中药组中均有所减轻,但基质组未见改善；剂量较高的中药组肾脏病变以肾小管及肾小管上皮细胞损伤为主,其中,RBP水平升高的A、B、C、D4个中药组肾小管上皮细胞肿胀明显,并有不同程度的脱落；A、B、C3组肾小管扩张明显.结论 常用肾功能检测指标不能较好的反映含汞中药外用制剂引起的早期肾脏病理损害,RBP可以在肾小管上皮细胞形态出现改变时较早地反映肾脏靶器官毒性.%Objection To study the changes of renal function indexes induced by repeated application of mercury-containing preparations of Chinese medicinals on skin ulcer and relationship between these changes and renal pathomorphology in rats, and provide evidences for monitoring the safety of mercury-containing preparations and definite diagnosis of renal injury. Methods SD rats (n - 80) were randomly divided into 8 groups, including skin damage ( control) group, model group, matrix group (vaseline) and 5 groups with different dose of preparations (1. 219 g/kg, 0.609 g/kg, 0. 305 g/kg, 0. 152 g/kg and 0.076 g/kg, group A, B, C, D and E). After consecutive medicinal administration for 14 days, the level of urinary retinol binding protein ( RBP) was detected by using enzyme-linked immunosorbent assay ( ELJSA) , level of blood urea nitrogen ( BUN) was detected by using urease method, and level of serum creatinine (SCr) was detected by using deproteinization method. The kidney coefficient was calculated through weighing fasting weight and organ net weight of rats. The renal pathomorphology was observed after fixing kidney with formalin solution and HE staining. Results Compared with model group, the levels of BUN and SCr had no changes in other groups. The level of RBP increased significantly in group A, B, C and D (P<0.01). The kidney coefficient increased to varying degrees in group A, B, C, D and E. The observation of renal pathomorphology showed that extensive wound, bacterial infection and inflammation could cause pathological changes of kidney, mainly renal interstitial hemorrhage and inflammatory cell infiltration. These pathological changes were relieved in group A, B, C, D and E, but not relieved in matrix group. In the groups with higher dose of preparations, the pathological changes were mainly injury of renal tubules and renal tubules epithelial cells. In group A, B, C and D with higher level of RBP, renal tubules epithelial cells swelled obviously and exfoliated in varying degrees. In group A, B and C, the ectasia of renal tubules was obvious. Conclusion The common detecting indexes for kidney function can not reflect early renal pathological damage induced by external mercury-containing preparations of Chinese medicinals, and RBP can reflect early the toxic damage of kidney,a target organ, when the morphology changes occur in renal tubules epithelial cells.
展开▼
