机构地区:[1]西安医学院药理学和毒理学教研室,陕西西安710021
出 处:《西安交通大学学报(医学版)》2022年第6期827-832,共6页Journal of Xi’an Jiaotong University(Medical Sciences)
基 金:博士科研启动基金资助项目(No.2017DOC15)。
摘 要:目的 观察3,4-二羟基-5-硝基苯甲醛(3,4-dihydroxy-5-nitrobenzaldehyde, DHNB)对小鼠及鹌鹑高尿酸血症模型的降尿酸作用,完善高尿酸血症模型的药效学验证。方法 氧嗪酸钾(potassium oxonate, PO)300 mg/kg腹腔注射制备小鼠高尿酸血症动物模型;30 g/(kg·d)的酵母粉混合饲料(酵母粉∶饲料为1∶4)制备鹌鹑高尿酸血症动物模型。于小鼠高尿酸血症模型造模前1 h腹腔注射DHNB 100 mg/kg;连续2 d灌胃DHNB 100 mg/kg处理鹌鹑高尿酸血症模型。另设对照组。生化试剂盒检测各组小鼠及鹌鹑血清尿酸(serum uric acid, SUA)、谷草转氨酶(aspartate aminotransaminase, AST)、谷丙转氨酶(alanine aminotransaminase, ALT)、肌酐(creatinine, Cr)和尿素氮(blood urea nitrogen, BUN)。取小鼠及鹌鹑的心、肺、肝和肾组织进行HE染色。结果 小鼠及鹌鹑高尿酸血症模型组SUA均高于对照组[(277.37±94.89)μmol/L vs.(176.49±44.83)μmol/L,P<0.05;(313.58±191.87)μmol/L vs.(167.26±66.56)μmol/L,P<0.05],提示造模成功。DHNB不能降低高尿酸血症小鼠模型SUA[(277.37±94.89)μmol/L vs.(238.72±63.43)μmol/L,P>0.05],但明显降低高尿酸血症鹌鹑模型SUA[(313.58±191.87)μmol/L vs.(160.44±49.90)μmol/L,P<0.05]。DHNB 100 mg/kg给药对小鼠和鹌鹑肝肾功无影响,且对小鼠和鹌鹑心、肺、肝和肾组织无毒性。结论 DHNB对高尿酸血症鹌鹑模型具有降尿酸作用,且单次给予降尿酸剂量对小鼠及鹌鹑脏器无明显毒性。鹌鹑高尿酸血症模型比小鼠高尿酸血症模型更适用于DHNB降尿酸药效的验证。Objective To observe the uric acid-lowering effect of 3,4-dihydroxy-5-nitrobenzaldehyde(DHNB) on hyperuricemia models in mice and quails so as to improve the pharmacodynamic validation on hyperuricemia models. Methods The mouse hyperuricemia animal model was prepared by intraperitoneal injection of potassium oxonate 300 mg/kg;30 g/(kg·d) yeast powder mixed feed(yeast powder∶feed, 1∶4) was used to prepare the quail hyperuricemia animal model. DHNB, 100 mg/kg, was intraperitoneally injected into the mice 1 hour prior to modeling;DHNB, 100 mg/kg, was intragastrically administered for two days consecutively into the quail hyperuricemia models. Control groups in mice and quails were set up respectively. Biochemical kits were used to detect serum uric acid, aspartate aminotransaminase(AST), alanine aminotransaminase(ALT), creatinine(Cr), and blood urea nitrogen(BUN) in mouse and quail serum. Heart, lung, liver and kidney tissues of mice and quails were stained with HE. Results The serum uric acid in the mouse and quail hyperuricemia model groups was higher than that in the control group [(277.37±94.89) μmol/L vs.(176.49±44.83) μmol/L, P<0.05;(313.58±191.87) μmol/L vs.(167.26±66.56) μmol/L, P<0.05)], indicating that the modeling was successful. DHNB could not reduce serum uric acid in hyperuricemia mouse model [(277.37±94.89) μmol/L vs.(238.72±63.43) μmol/L, P>0.05]. However, it significantly decreased serum uric acid in the quail model of hyperuricemia(313.58±191.87) μmol/L vs.(160.44±49.90)μmol/L, P<0.05]. Administration of DHNB 100 mg/kg one or two times had no effect on the liver and kidney functions of mice and quails, and had no toxicity to the heart, lung, liver or kidney tissues of mice and quails. Conclusion DHNB has a uric acid-lowering effect on the hyperuricemia quail model, and a single dose that caused the uric acid-lowering effect has no obvious toxicity to mouse or quail viscera. The quail hyperuricemia model is more suitable for the validation of the uric acid-lowering efficacy of D
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