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河南中医药大学 药学院,郑州 450046
白莉,博士,副教授,从事中药药理研究,E-mail:baili64@163.com
苗明三,博士,教授,博士生导师,从事中药药理研究,E-mail:miaomingsan@163.com
纸质出版日期:2022-09-20,
网络出版日期:2022-03-07,
收稿日期:2021-11-29,
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白莉,刘广运,张晓萍等.牡丹花总黄酮对高尿酸血症大鼠降尿酸作用[J].中国实验方剂学杂志,2022,28(18):38-45.
BAI Li,LIU Guangyun,ZHANG Xiaoping,et al.Effect of Total Flavonoids in Flower of Paeonia suffruticosa on Uric Acid in Rats with Hyperuricemia[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):38-45.
白莉,刘广运,张晓萍等.牡丹花总黄酮对高尿酸血症大鼠降尿酸作用[J].中国实验方剂学杂志,2022,28(18):38-45. DOI: 10.13422/j.cnki.syfjx.20220905.
BAI Li,LIU Guangyun,ZHANG Xiaoping,et al.Effect of Total Flavonoids in Flower of Paeonia suffruticosa on Uric Acid in Rats with Hyperuricemia[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):38-45. DOI: 10.13422/j.cnki.syfjx.20220905.
目的
2
探究牡丹花总黄酮对高尿酸血症大鼠的药效学作用,为高尿酸血症治疗药物的研究开发提供科研数据支撑。
方法
2
使用腺嘌呤合并乙胺丁醇复制大鼠高尿酸血症模型,大鼠随机分为正常组、模型组、别嘌醇组(42 mg·kg
-1
)、痛风舒片组(600 mg·kg
-1
)、牡丹花总黄酮高、中、低剂量组(TFPF 260、130、65 mg·kg
-1
)。记录观察大鼠状态,每5 d记录一次大鼠体质量;测定末次给药24 h大鼠尿量、饮水量、尿液中尿酸(UA)、尿蛋白水平;计算大鼠肾脏指数;苏木素-伊红(HE)染色法观察大鼠胸腺、脾脏组织;测定大鼠血清中尿酸(UA)、肌酐(Cr)、血尿素氮(BUN)、丙二醛(MDA)、超氧化物歧化酶(SOD)活力、总抗氧化能力(T-AOC)活力;测定大鼠肝脏中黄嘌呤氧化酶(XOD)、腺苷脱氨酶(ADA)活性;酶联免疫吸附测定法(ELISA)检测大鼠肾脏中尿酸转运体1(URAT1)、阴离子转运蛋白1(OAT1)、葡萄糖转运蛋白9(GLUT9)含量。
结果
2
与模型组比较,牡丹花总黄酮可改善大鼠精神状态,增加大鼠体质量(
P
<
0.01)、促进大鼠尿液尿酸排泄(
P
<
0.01),降低尿蛋白量(
P
<
0.05);降低大鼠24 h尿量、饮水量、肾脏脏器指数(
P
<
0.05)、血清中UA、Cr、BUN、MDA含量(
P
<
0.05,
P
<
0.01);抑制肝脏中XOD(
P
<
0.05)、ADA活性(
P
<
0.05,
P
<
0.01);减少肾匀浆GLUT9表达量(
P
<
0.05);提高血清SOD和T-AOC活性及肾脏中OAT1表达量(
P
<
0.01);改善大鼠胸腺和脾脏病理变化。
结论
2
牡丹花总黄酮对高尿酸血症大鼠肾脏具有一定的保护作用,其作用与促进尿酸排泄,抑制氧化反应,抑制尿酸合成关键酶活性,调节尿酸转运蛋白表达有关。
Objective
2
To explore the pharmacodynamic effects of total flavonoids of
Paeonia suffruticosa
flower (TFPFs) on rats with hyperuricemia and provide scientific data support for the research and development of therapeutic drugs for hyperuricemia.
Method
2
The hyperuricemia model was induced by adenine combined with ethambutol in rats. The rats were randomly divided into a blank control group, a model group, two positive control groups (allopurinol at 42 mg·kg
-1
and Tongfengshu tablets at 600 mg·kg
-1
), and high-, medium-, and low-dose TFPFs groups (260, 130, and 65 mg·kg
-1
). The general conditions of rats were observed and recorded, and the body weight was recorded once every 5 days. The 24-hour urine volume, water intake, uric acid (UA), and urinary protein of rats were determined after the last administration. The kidney index was calculated. The pathological changes in thymus and spleen tissues of rats were observed by hematoxylin-eosin (HE) staining. The serum activities of UA, creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) of rats were determined. The xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were detected. The content of uric acid transporter 1 (URAT1), organic anion transporter 1 (OAT1), and glucose transporter 9 (GLUT9) in the kidney was detected by enzyme-linked immunosorbent assay (ELISA).
Result
2
Compared with the results in the model group, TFPFs could improve the mental state of rats, increase the body weight(
P
<
0.01), promote UA excretion(
P
<
0.01), reduce the content of urinary protein(
P
<
0.05), relieve renal glomerular atrophy, renal tubular epithelial cell status, and urate crystal deposition in renal tubules, dwindle 24-hour urine volume, water intake, kidney index(
P
<
0.05), serum levels of UA, Cr, BUN, and MDA(
P
<
0.05,
P
<
0.01), inhibit the activities of XOD(
P
<
0.05) and ADA(
P
<
0.05,
P
<
0.01)in the liver, diminish the expression of GLUT9 in the renal homogenate(
P
<
0.05), and increase serum SOD and T-AOC activities as well as OAT1 expression(
P
<
0.01) in the kidney. The pathological changes of thymus and spleen were improved.
Conclusion
2
TFPFs possess a protective effect on the kidney of rats with hyperuricemia, which is achieved by promoting uric acid excretion, inhibiting oxidation and the activity of key enzymes in uric acid synthesis, and regulating the expression of uric acid transporters.
高尿酸血症牡丹花总黄酮尿酸尿酸转运蛋白
hyperuricemiaPaeonia suffruticosa flowertotal flavonoidsuric aciduric acid transporter
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