|
|
急性马兜铃酸I中毒小鼠肾小管上皮细胞损伤变化
|
Abstract:
为连续观察急性马兜铃酸I (Aristolochic Acids I, AAI)中毒时小鼠肾脏病理学改变，本实验将40只KM小鼠分为5组：对照组、AAI暴露2、4、6、8天组，AAI组小鼠以5 mg/kg/2d AAI灌胃模拟急性马兜铃酸肾病(Aristolochic Acid Nephropathy, AAN)，使各组小鼠AAI累积剂量分别为5、10、15、20 mg/kg。分别于AAI暴露2、4、6、8天处死，检测其肾功能指标肌酐(Creatinine, Cre)和尿素氮(Blood Urea Nitrogen, BUN)，并观察肾脏病理学改变。结果显示，与对照组相比，AAI各组小鼠Cre和BUN均呈剂量依赖性上升，Cre于第6、8天具有显著性差异(P < 0.05)；BUN于第4、6、8天具有显著性差异(P < 0.05)。AAI组小鼠主要病理变化为肾小管上皮细胞顶端微绒毛脱落、细胞水肿、坏死脱落。本研究发现暴露于AAI的小鼠肾小管损伤程度与AAI累积剂量呈正相关。
In order to continuously observe the renal pathological changes in mice during acute aristolochic acids I (AAI) intoxication, 40 KM mice were divided into 5 groups: control group, AAI exposed for 2, 4, 6, and 8 days, and mice in the AAI group were simulated with acute aristolochic acid nephropathy (AAN) by gavage of 5 mg/kg/2d AAI, and the cumulative dose of AAI in each group was 5, 10, 15, and 20 mg/kg, respectively. Mice in the AAI group were put to death on 2, 4, 6, and 8 days of exposure to AAI to test their renal function indexes of creatinine (Cre) and blood urea nitrogen (BUN) and to observe the renal pathological changes. The results showed that compared with the control group, Cre and BUN increased in a dose-dependent manner in the AAI group, with significant differences in Cre on days 6 and 8 (P < 0.05) and BUN on days 4, 6 and 8 (P < 0.05). The main pathological changes in the AAI group were detachment of microvilli from the tips of renal tubular epithelial cells, cellular edema, and necrotic detachment. In this study, we found that the degree of renal tubular injury in mice exposed to AAI was positively correlated with the cumulative dose of AAI.
| [1] | Xu, T., Chen, W., Zhou, J., et al. (2021) Computational Analysis of Naturally Occurring Aristolochic Acid Analogues and Their Biological Sources. Biomolecules, 11, 1344. https://doi.org/10.3390/biom11091344 |
| [2] | 何曼文, 郭海嘉, 黎芷君, 等. HPLC法对鱼腥草中马兜铃酸A的定性分析[J]. 山东化工, 2022, 51(24): 111-113. |
| [3] | 赖珊, 李菌芳, 袁干军, 等. 青木香的仿生炮制减毒研究[J]. 时珍国医国药, 2021, 32(7): 1647-1650. |
| [4] | 文星星, 张朝辉, 刘可钦, 等. 含马兜铃酸中药的减毒存效研究进展[J]. 工业微生物, 2023, 53(5): 68-70. |
| [5] | 王婉丽, 樊馨, 杨亚彬, 等. 倒心盾翅藤抗炎活性部位对马兜铃酸肾病大鼠肾脏的保护作用[J]. 中成药, 2023, 45(10): 3442-3446. |
| [6] | Zhang, H.M., Zhao, X.H., Sun, Z.H., et al. (2019) Recognition of the Toxicity of Aristolochic Acid. Journal of Clinical Pharmacy and Therapeutics, 44, 157-162. https://doi.org/10.1111/jcpt.12789 |
| [7] | Dong, Y.P., Chen, S.Z., He, H.S., et al. (2023) Skullcapflavone II, a Novel NQO1 Inhibitor, Alleviates Aristolochic Acid I-Induced Liver and Kidney Injury in Mice. Acta Pharmacologica Sinica, 44, 1429-1441. https://doi.org/10.1038/s41401-023-01052-3 |
| [8] | 王一凡, 刘爽, 汪思齐, 等. 急性马兜铃酸中毒小鼠肾损伤及Wnt7b/β-catenin/MMP-7的表达变化[J]. 中国医科大学学报, 2023, 52(6): 505-511. |
| [9] | Ji, H., Hu, J., Zhang, G., et al. (2021) Aristolochic Acid Nephropathy: A Scientometric Analysis of Literature Published from 1971 to 2019. Medicine, 100, e26510. https://doi.org/10.1097/MD.0000000000026510 |
| [10] | Feng, C., Anger, E.E., Zhang, X., et al. (2022) Protective Effects of Mitochondrial Uncoupling Protein 2 against Aristolochic Acid I-Induced Toxicity in HK-2 Cells. International Journal of Molecular Sciences, 23, 3674. https://doi.org/10.3390/ijms23073674 |
| [11] | Jiang, Z., Bao, Q., Sun, L., et al. (2013) Possible Role of mtDNA Depletion and Respiratory Chain Defects in Aristolochic Acid I-Induced Acute Nephrotoxicity. Toxicology and Applied Pharmacology, 266, 198-203. https://doi.org/10.1016/j.taap.2012.07.008 |
| [12] | Wald, R., Kirkham, B., Dacosta, B.R., et al. (2022) Fluid Balance and Renal Replacement Therapy Initiation Strategy: A Secondary Analysis of the STARRT-AKI Trial. Critical Care (London, England), 26, Article No. 360. https://doi.org/10.1186/s13054-022-04229-0 |
| [13] | Bohn, M.K., Higgins, V. and Adeli, K. (2020) CALIPER Paediatric Reference Intervals for the Urea Creatinine Ratio in Healthy Children & Adolescents. Clinical Biochemistry, 76, 31-34. https://doi.org/10.1016/j.clinbiochem.2019.12.001 |
| [14] | Liu, X., Wu, J., Wang, J., et al. (2020) Mitochondrial Dysfunction Is Involved in Aristolochic Acid I-Induced Apoptosis in Renal Proximal Tubular Epithelial Cells. Human & Experimental Toxicology, 39, 673-682. https://doi.org/10.1177/0960327119897099 |
| [15] | Li, X.W., Yokota, S., Wang, D., et al. (2014) Localization of Aristolochic Acid in Mouse Kidney Tissues by Immunohistochemistry Using an Anti-AA-I and AA-II Monoclonal Antibody. The American Journal of Chinese Medicine, 42, 1453-1469. https://doi.org/10.1142/S0192415X14500918 |
