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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、D 4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、C 3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。
Objective To study the relationship between changes of renal function indexes and pathological changes of kidney induced by repeated administration of mercury-containing Chinese herbal preparations on the skin of rats with ulcer, and to provide evidence for clinical monitoring of the safety of mercury-containing preparations and the definite diagnosis of renal damage. Methods 80 SD rats were randomly divided into 8 groups: skin lesion group, ulcer model group, matrix group (Vaseline) and five Chinese medicine groups A, B, C, D and E (1.219,0.609,0.305,0.152,0.076 g / kg). Serum urea nitrogen (BUN) was detected by enzyme-linked immunosorbent assay (ELISA) and serum creatinine (SCr) by protein removal assay. Body weight and wet weight of the organ were calculated, and the renal coefficient was calculated. The formalin-fixed kidney was used for HE staining to observe the morphology of kidney. Results Compared with the ulcer model group, there was no abnormality of BUN and SCr in each group. The RBP levels in Chinese medicine groups A, B, C and D were significantly increased (P <0.01). The renal coefficient of each TCM group was increased to some extent. Morphological observation of kidney showed that large area of trauma, bacterial infection and inflammation and other pathological factors can cause renal lesions in rats with ulceration model, with interstitial hemorrhage and inflammatory cell infiltration, and this pathological damage in the Chinese medicine group were , But there was no improvement in the matrix group. The renal lesion in the traditional Chinese medicine group with higher dose was mainly characterized by renal tubular and renal tubular epithelial cell injury, in which the renal tubules of the four TCM groups (A, B, C and D) Epithelial cells obviously swollen, and have different degrees of exfoliation; A, B, C group of tubular dilatation significantly. Conclusion Common renal function tests can not reflect the early stage of renal pathological damage caused by topical preparations containing mercury, and RBP can reflect the target organ toxicity earlier when the morphology of renal tubular epithelial cells changes.