Li Qing-Qing, Yang Bin, Chen Na, Gong Lei-Lei, Liang Ri-Xin, Wang Lan, Yin Xiao-Jie
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine Ji'nan 250355, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(23):6431-6437. doi: 10.19540/j.cnki.cjcmm.20220727.402.
To explore the effect of the granules made by new-medicinal parts of Crocus sativus(NMPCS) on hyperuricemia(HUA) in rats, the rat model of HUA was established by intramuscular injection of 3% potassium oxonate and intraperitoneal injection of 4% pyrazinamide. The content of serum uric acid was monitored every week for 3 consecutive weeks. After the experiment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen(BUN), and xanthine oxidase(XOD) were determined. The protein and gene expressions of XOD were determined by Western blot method and fluorescence quantitative polymerase chain reaction(qPCR), and the morphological changes in the liver tissue were performed by hematoxylin-eosin(HE) staining. The results showed that as compared with the model group, the levels of serum uric acid in the positive drug group and the low, medium, and high-dose NMPCS groups were lower(P<0.05), the levels of urine uric acid in the high-dose NMPCS group were decreased(P<0.01), and there was no statistical difference in the medium and low-dose NMPCS groups. The levels of BUN in the high and low-dose NMPCS groups were decreased(P<0.05), and the levels of serum creatinine did not change in the administration groups. The positive drug group and the low, medium, and high-dose NMPCS groups significantly reduced the liver damage, with only a few hepatocytes vacuolization and a small number of red blood cells in the central venous area. The nephridial tissue structure was slightly abnormal, with a small number of red blood cell infiltration, and no obvious inflammatory cell infiltration was found in the glomerulus in these groups. No degeneration was found in renal tubular epithelial cells, with mild glomerular and tubular lesions and a small amount of sodium urate deposition and crystallization in the positive drug group and the low, medium, and high-dose NMPCS groups. The relative protein expressions of XOD in the positive drug group and the high dose NMPCS group were decreased(P<0.05), and the relative mRNA expressions of XOD in the positive drug group and the high and low-dose NMPCS groups were decreased as well(P<0.05). The above results show that NMPCS reduces uric acid in rats with HUA by regulating XOD, which provides a certain experimental basis for the development of NMPCS as a new medicine for the treatment of HUA.
为探讨西红花新药用部位制成的颗粒剂（NMPCS）对大鼠高尿酸血症（HUA）的影响，采用肌肉注射3%氧嗪酸钾和腹腔注射4%吡嗪酰胺的方法建立大鼠HUA模型。连续3周每周监测血清尿酸含量。实验结束后，测定血清尿酸、尿尿酸、血清肌酐、血尿素氮（BUN）和黄嘌呤氧化酶（XOD）水平。采用蛋白质印迹法和荧光定量聚合酶链反应（qPCR）检测XOD的蛋白和基因表达，并用苏木精-伊红（HE）染色观察肝组织形态学变化。结果显示，与模型组相比，阳性药物组及NMPCS低、中、高剂量组血清尿酸水平降低（P<0.05），NMPCS高剂量组尿尿酸水平降低（P<0.01），NMPCS中、低剂量组无统计学差异。NMPCS高、低剂量组BUN水平降低（P<0.05），给药组血清肌酐水平无变化。阳性药物组及NMPCS低、中、高剂量组均显著减轻肝脏损伤，中央静脉区仅有少数肝细胞空泡化和少量红细胞。肾组织结构轻度异常，有少量红细胞浸润，各组肾小球均未发现明显炎性细胞浸润。肾小管上皮细胞未见变性，阳性药物组及NMPCS低、中、高剂量组肾小球和肾小管病变轻微，有少量尿酸钠沉积和结晶。阳性药物组及NMPCS高剂量组XOD相对蛋白表达降低（P<0.05），阳性药物组及NMPCS高、低剂量组XOD相对mRNA表达也降低（P<0.05）。上述结果表明，NMPCS通过调节XOD降低HUA大鼠尿酸水平，为NMPCS开发成为治疗HUA的新药提供了一定的实验依据。
