本研究以KM小鼠作为实验动物，研究2.5 μM、5.0 μM、7.5 μM、10 μM、15 μM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 μM和10 μM 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。这一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。

Patulin (PAT) is a toxic secondary metabolite produced by Penicillium and Aspergillus . At present, toxicological studies on PAT mainly include the toxicity to the liver, the intestines, the stomach and the skin. However, there are few studies on the toxicity to the kidneys. Therefore, in this study, KM mice were used as experimental animals. At concentration gradients of 2.5 μM, 5.0 μM, 7.5 μM, 10 μM and 15 μM for PAT, the body weight and renal coefficient in mice would be recorded. In addition, kidney section staining experiments would be used to verify the damage of PAT to the kidneys. There was no effect of PAT concentration on body weight growth rate. However, as the concentration of PAT increased, the kidney coefficient tended to increase gradually, and the difference between 7.5 μM and 10 μM PAT treatment was significant (p<0.05). As the concentration of PAT increased, a large area of cell stroma and extracellular matrix could be observed after HE staining (hematoxylin-eosin staining). The bluish purple nuclei are gradually reduced. And the nucleus density gradually decreases. In addition, there were long blanks at higher PAT concentrations. Glomeruli showed marked fibrosclerosis after staining with Masson. There is also congestion between the cells. A small amount of glycogen appeared after staining with Periodic Acid-Schiff (PAS), which indicates that glycogen was not properly degraded. Therefore, the increase in PAT concentration led to the decrease in nucleus density, the shrinkage of kidney cells, the increase in collagen fibers and inhibition of glycogen breakdown.Consequently, it can cause severe kidney damage in KM mice.This result will provide theoretical support for further studies on kidney damage caused by patulin.

国家自然基金、甘肃省自然基金