甘草酸和泼尼松对慢性马兜铃酸肾病大鼠肾脏组织病理及超微病理改变的影响

Effects of Glycyrrihizic Acid and Prednisone on Pathological and Ultrastructural Changes of Kidney in Rats with Chronic Aristolochic Acid Nephropathy

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中文关键词: 马兜铃酸肾脏病甘草酸

英文关键词:aristolochic acid renal disease glycyrrihizic acid

基金项目:上海市自然科学基金资助项目(No.03ZR14031);上海市青年科技启明星基金资助项目(No．04QMX1453)

作者	单位
王会玲	上海解放军第四五五医院肾脏科南京军区肾脏病专科中心上海 200052
张金元	上海解放军第四五五医院肾脏科南京军区肾脏病专科中心上海 200052
黄健	上海解放军第四五五医院肾脏科南京军区肾脏病专科中心上海 200052

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中文摘要:

目的通过建立大鼠慢性马兜铃酸肾病(AAN)动物模型,观察甘草酸、泼尼松对慢性AAN肾损害的干预作用。方法雄性Wistar大鼠98只,SPF级,随机分为4组:正常对照组20只,模型组、甘草酸组、泼尼松组每组26只;实验组按马兜铃酸(AA)20 mg／(kg·d)关木通浸膏灌胃,正常对照组灌胃等体积饮用水;2 h后按分组灌胃给药:甘草酸25 mg／(kg·d),泼尼松3．15 mg／(kg·d);正常对照组、模型组灌胃饮用水。各组每周测量体重,于第4、8、12周测定相关肾功能指标;取肾组织进行形态学检查。结果随着喂饲时间延长,正常对照组大鼠体重稳定性增长,而马兜铃酸给药各组体重增长缓慢。马兜铃酸用药后各组血肌酐／体重水平明显增高,甘草酸组、泼尼松组血肌酐／体重水平显著降低。肾脏组织形态学改变:甘草酸、泼尼松治疗组形态结构损害程度较模型组(纤维化程度约30％)轻微,纤维化程度约15%-20%。电镜结果:马兜铃酸可引起肾小管上皮细胞损伤、变性、坏死,线粒体等细胞器损伤明显,有细胞核变异。甘草酸、泼尼松组以小管损伤为主,线粒体等细胞器正常,细胞核变异少见,间质胶原纤维较少。结论甘草酸、泼尼松对大鼠慢性马兜铃酸肾损害有一定的保护作用,能降低血肌酐,改善肾功能,在一定程度上减轻马兜铃酸造成的肾组织形态学改变,并减少肾间质纤维化程度。

英文摘要:

Objective To investigate the effects of glycyrrihizic acid (GA) and prednisone on renal injury in chronic aristolochic acid nephropathy (AAN) rat model. Methods Ninety-eight male Wistar rats of SPF grade were randomly divided into 4 groups, the normal control group (n = 20), the GA group, the model group, and the prednisone group, 26 rats in each group. Rats in the latter 3 groups were made into AAN model by administration of aristolochic acid (AA, contained in extract of Caulis Aristolochiae Manshuriensis) 20 mg/(kg·d) by gastric gavage, and equal volume of drinking water was given to rats in the control group. Medication was started 2 h later, the GA group was treated with GA 25 mg/(kg·d), the prednisone group with prednisone 3. 15 mg/(kg·d) ,and to the other two groups equal volume of drinking water was given. Body weight was measured weekly, renal function related indices and morphology of the renal tissue were examined at the 4th, 8th and 12th weekend. Results Along with the feeding time, body weight in the control group increased steadily, while that in the treated groups increased slowly. The ratio of serum creatinine/body weight increased markedly in the model group, while it significantly lowered in the treated groups. Morphological examination showed that the structural injury in the treated groups was milder than that in the model group, and its degree of fibrosis was milder also (15% - 20% vs 30%). Electronmicroscopy showed that AA induced, injury degeneration and necrosis of renal tubular epithelial cells, and markedly injured the cell organs, such as mitochondria, and induced nuclear variation, while in the treated groups, it was mainly limited in renal tubule, with normal cell organs, few nucleolus variation and less interstitial collagen fibers. Conclusion GA and prednisone could reduce the serum creatinine level, improve renal function, relieve the renal morphological changes, and decrease the interstitial fibrosis, showing a definite preventing effect on chronic AAN in rats.

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