1.宜兴市人民医院泌尿外科，江苏 宜兴 214222 ;2.南京医科大学第二附属医院泌尿外科，江苏，南京 210003 ;3.南京医科大学第一附属医院泌尿外科，江苏 南京 210029
无锡市卫生健康委科研项目（M202241）
1.Department of Urology，Yixing People’s Hospital，Yixing 214222 ;2.Department of Urology，the Second Affiliated Hospital of Nanjing Medical University，Nanjing 210003 ;3.Department of Urology，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029 ，China
目的：探究广金钱草总黄酮（total flavonoids of Desmodium styracifolium，TFDS）对肾草酸钙结石形成的作用及可能机制。方法：构建选择性巨噬细胞mTOR复合物2的RPTOR独立伴侣（RPTOR independent companion of mTOR complex 2，Rictor） 基因敲除小鼠（Rictorfl/flCre+ ）及其对照组小鼠（Rictorfl/flCre- ）的肾草酸钙结石模型，并给予TFDS干预。收集各组小鼠肾组织行 HE染色、免疫组织化学荧光染色、流式细胞术等检查，探讨TFDS对小鼠肾草酸钙结石形成的影响；原代提取上述两种小鼠的骨髓来源巨噬细胞（bone marrow derived macrophage，BMDM），分别给予TFDS干预，通过PCR、细胞荧光染色、流式细胞术等检探究上述机制。结果：Rictorfl/flCre+ 组小鼠的肾组织中肾草酸钙结石数目显著多于Rictorfl/flCre-组，并伴随M1型巨噬细胞极化明显增多；TFDS干预两组小鼠后，TFDS+Rictorfl/flCre-组的肾组织中肾草酸钙结石及M1型巨噬细胞极化均显著降低，而TFDS+ Rictorfl/flCre+ 组的肾草酸钙结石形成较Rictorfl/flCre+ 组无明显变化。细胞实验表明，Rictor敲除后的BMDM出现了显著的M1型巨噬细胞极化，TFDS干预未敲除Rictor的BMDM组中的M1型巨噬细胞极化明显减少；而TFDS干预后Rictor敲除的BMDM极化较干预前无显著变化。结论：TFDS有效且安全地减少肾草酸钙结石的形成可能与抑制Rictor调控的M1型巨噬细胞极化有关。
Objective：To investigate the effect and possible mechanism of total flavonoids of Desmodium styracifolium（TFDS）on the formation of renal calcium oxalate stones. Methods：The selective macrophage Rictor gene knockout mice（Rictorfl/flCre+ ）and their control group mice（Rictorfl/flCre- ）were used to establish renal calcium oxalate stone models，and the TFDS intervention was administered to the mice. We collected the kidney tissues from these two groups of mice for HE staining，immunohistochemical fluorescence staining，flow cytometry to explore the effect of TFDS on the formation of renal calcium oxalate stones. Primary bone marrow-derived macrophage（BMDM）from the two types of mice was extracted，and TFDS intervention was administered to investigate the mechanism through PCR，cell fluorescence staining，flow cytometry. Results：The number of renal calcium oxalate stones of the Rictorfl/flCre+ mice was significantly higher than that in the Rictorfl/flCre- mice，accompanied by a significant increase in the polarization of M1 macrophages. After TFDS intervention in two groups of mice，the renal tissue of the TFDS + Rictorfl/flCre- group showed a significant decrease in renal calcium oxalate stones and M1 macrophage polarization，while the formation of renal calcium oxalate stones in the TFDS+Rictorfl/flCre+ group showed no significant changes compared with the Rictorfl/flCre- group. Cell experiments showed that after the Rictor knockout，BMDM exhibited significant polarization of M1 macrophages，while the polarization of M1 macrophages was significantly reduced in the TFDS+BMDM group；however，there was no significant change in polarization after TFDS intervention in Rictor knockout of BMDM compared with that before intervention. Conclusion：TFDS may effectively and safely reduce the formation of renal calcium oxalate stones，possibly by inhibiting the Rictor regulated polarization of M1 macrophages.
宗益平,张俊麒,王子杰,韩鹏,张炜,鲁佩.广金钱草总黄酮抑制M1型巨噬细胞极化减少小鼠肾草酸钙结石形成[J].南京医科大学学报（自然科学版）,2025,(3):327-333
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