Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C–X–C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.

虽然原发性膀胱结石是一种古老的疾病，但结石形成的机制仍不清楚。在本研究中，我们用d , l-酒石酸胆碱在小鼠体内建立了一种新的原发性膀胱结石模型。与常用的三聚氰胺和乙二醇模型相比，我们的模型是唯一一种诱导膀胱结石而不造成肾损伤的方法。先前的研究表明，日常饮食中的蛋白质是预防膀胱结石的主要因素，但脂肪的作用却被忽视了。测定膳食脂肪与原发性膀胱结石形成的关系，d，l用酒石酸胆碱处理的小鼠喂食高脂肪、低脂肪或正常脂肪饮食。用转录组分析检测小鼠膀胱的遗传变化。高脂肪饮食显着降低了原发性膀胱结石的发病率。与正常和低脂饮食组相比，高脂饮食组血清和尿液中的脂肪酸水平较高，同组膀胱内的完整上皮细胞更丰富，提示脂肪酸对机体的保护作用。膀胱上皮细胞维持其正常的组织学结构。转录组分析显示巨噬细胞分化相关基因 C–X–C 基序趋化因子配体 14 ( Cxcl14) 在高脂饮食喂养小鼠的膀胱中与正常或低脂饮食喂养小鼠的膀胱相比上调，这与组织学观察结果一致。高脂饮食组膀胱中CXCL14的表达显着增加。CXCL14增强巨噬细胞向晶核的募集并诱导M2巨噬细胞的转化，从而导致出芽晶体的吞噬作用并防止结石的积累。在人膀胱上皮 (HCV-29) 细胞中，高脂肪酸补充显着增加了 CXCL14 的表达。膳食脂肪对于维持膀胱生理功能和预防原发性膀胱结石至关重要，为降低原发性膀胱结石的发病率提供了新思路。