该研究以KM小鼠作为实验动物，研究2.5、5.0、7.5、10、15 μmol/L五个浓度梯度下棒曲霉素对小鼠体重、肾脏系数等的影响，并通过各项肾脏切片染色试验验证PAT对肾脏的毒性损伤。其中PAT浓度对体重增长率基本无影响，两者之间几乎无相关关系；而随着PAT浓度增大，肾脏系数有逐渐增大的趋势，其中7.5 μmol/L和10 μmol/L PAT处理的差异显著（p<0.05）；随着PAT浓度增加，苏木素-伊红（hematoxylin-eosin，HE）染色后可观察到大片细胞基质和胞外基质，蓝紫色细胞核逐渐减少且细胞核密度逐渐降低，此外PAT浓度较高时出现了长条状空白；Masson染色后肾小球发生明显的纤维硬化情况，且胞间充血；过碘酸雪夫（Periodic Acid-Schiff，PAS）染色后出现了少量糖原，可知糖原没有被正常降解。因此，PAT浓度的增加会导致核密度降低、肾脏细胞皱缩、胶原纤维增加、糖原分解被抑制等问题，从而对KM小鼠肾脏造成严重损伤。研究结果将为进一步研究棒曲霉素对肾脏的损伤提供理论支持。

In this study, KM mice were used as experimental animals. The effects of patulin (PAT) at concentration gradients of 2.5, 5.0, 7.5, 10 and 15 μmol/L on the body weight and renal coefficients in mice were investigated. The toxicity and damage of PAT to the kidneys were examined through section staining experiments. The PAT concentration had little effect on the increasing rate of body weight, and there was almost no correlation between them. However, as the concentration of PAT increased, the kidney coefficients tended to increase gradually, with the difference between the 7.5 μmol/L PAT treatment and 10 μmol/L PAT treatment being significant (p<0.05). As the concentration of PAT increased, large areas of cell stroma and extracellular matrix were observed after HE staining (hematoxylin-eosin staining), with the number of bluish purple nuclei and the nucleus density gradually decreasing. In addition, there were long blank strips at higher PAT concentrations. After Masson staining, glomeruli showed sinificant fibrosclerosis, along with intercellular congestion. A small amount of glycogen appeared after periodic acid-schiff (PAS) staining, indicating that glycogen was not normally degraded. Therefore, the increase in PAT concentration led to problems such as decreased nucleus density, shrinkage of kidney cells, increased collagen fibers and inhibition of glycogenolysis, causing severe kidney damage in KM mice. This result will provide theoretical support for further studies on the damage of PAT to the kidney.

国家自然科学基金项目（31760495）；甘肃省自然科学基金项目（18JR3RA136）