目的 探讨黄葵四物方对尿毒素分子硫酸对甲酚（p-cresyl sulfate，PCS）在宿主细胞内的代谢通路及转运环节的影响，并初步探讨其作用机制。方法 采用超高效液相色谱-三重四级杆质谱仪（ultra performance liquid chromatography-triple quadrupole/mass spectrometry，UPLC-TQ/MS）检测黄葵四物方干预后血浆及脏器内PCS水平的变化。采用酶活法检测肝脏内PCS合成酶磺基转移酶的活力。采用qRT-PCR及Western blotting检测结肠和肝脏中磺基转移酶及肾脏中有机阴离子转运体的基因转录和蛋白表达水平。结果 黄葵四物方可降低动物血浆或肝脏中PCS水平。黄葵四物方显著下调肝脏内磺基转移酶基因转录和蛋白表达水平（P<0.05），抑制肝脏中对甲酚向PCS转化，从而抑制宿主体内尿毒素分子PCS的合成。黄葵四物方不影响肾脏中有机阴离子转运体的基因转录和蛋白表达水平，不影响PCS由血液向肾脏中的转运过程。结论 黄葵四物方可通过调控宿主细胞内PCS的合成途径，抑制PCS体内合成，减少尿毒素蓄积，从而延缓慢性肾病进程。

Objective To investigate the effect and mechanism of action of Huangkui Siwu Formula (HKSWF, 黄葵四物方) on synthesis and transport pathways of urotoxin p-cresyl sulfate (PCS) in vivo. Methods The concentration of PCS in plasma and organs interfered by HKSWF were determined by ultra performance liquid chromatography-triple quadrupole/mass spectrometry (UPLC-TQ/MS). Enzyme activity method was used to detect the activity of sulfotransferase1a1 (SULT1A1). The gene transcription and protein expression of SULT1A1, organic anion transporter 1 (OAT1), and organic anion transporter 3 (OAT3) were tested by qRT-PCR and Western blotting. Results HKSWF could inhibit the conversion of p-cresol to PCS in the liver by significantly down-regulating SULT1A1 gene transcription and protein expression levels (P<0.05), thereby interfering the synthesis of PCS in the host cell. The gene transcription and protein expression levels of organic anion transporters in the kidney were not affected by HKSWF, and HKSWF did not affect the transportation of PCS into the kidney. Conclusion HKSWF can inhibit the formation of harmful urotoxin PCS by modulating the synthesis pathway of PCS in vivo and thereby delaying chronic kidney disease (CKD) progression.

R285

国家自然科学基金资助项目（81773983）；江苏省研究生科研与实践创新计划项目（KYCX19_1315）