白芍总苷对高尿酸血症并发肝脏损伤的保护作用

何欣宇; 刘冬恋; 李张悦; 陈汝梦; 陈梁; 秦星宇; 张倩

doi:10.13386/j.issn1002-0306.2022060082

白芍总苷对高尿酸血症并发肝脏损伤的保护作用

doi: 10.13386/j.issn1002-0306.2022060082

成都医学院药学院，四川成都 610500

基金项目: 大学生创新创业训练计划项目（S201913705037，202113705006）；四川养老与老年健康协同创新中心资助项目（19Z08）。

详细信息

作者简介:
何欣宇（2000−），女，大学本科，研究方向：药学，E-mail：1509562007@qq.com

通讯作者:
刘冬恋（1983−），女，硕士，高级实验师，研究方向：内分泌代谢性疾病及其并发症，E-mail: wushixian1992@foxmail.com

中图分类号: R285.5
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- 被引次数: 0
出版历程
- 收稿日期: 2022-06-10
- 网络出版日期: 2023-05-06
- 刊出日期: 2023-06-01

Protective Effect of Total Glucosides of Peony on Treatment of Hyperuricemia and Associated Hepatic Injury

Department of Pharmacy, Chengdu Medical College, Chengdu 610500, China

摘要

摘要: 目的：探讨白芍总苷（total glucosides of paeony，TGP）对大鼠高尿酸血症并发肝脏损伤的保护作用。方法：将50只雄性Sprague-Dawley大鼠随机分为5组：正常组、模型组、TGP低剂量组（100 mg/kg）、TGP高剂量组（300 mg/kg）和别嘌醇组（27.0 mg/kg），每组10只。模型组、TGP低、高剂量组和别嘌醇组大鼠分别按照1.5 mL/100 g的体积灌胃腺嘌呤6.66 mg/mL+氧嗪酸钾100 mg/mL的混合液制造高尿酸血症大鼠模型，每日7:00和20:00各1次，持续3周。每日12:00按剂量分别灌胃给药TGP和别嘌醇，持续5周。5周后，处死大鼠，检测各组大鼠的肝脏脏器指数，血清中总胆固醇（total cholesterol，TC）、甘油三酯（triglyceride，TG）、丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）、谷草转氨酶（aspartate aminotransferase，AST）、谷丙转氨酶（alanine aminotransferase，ALT）、尿酸和黄嘌呤氧化酶（xanthine oxidase，XOD）等生化指标，同时对肝脏进行病理切片观察。结果：高、低剂量TGP均能极显著增加高尿酸血症大鼠的肝脏脏器指数（P<0.01）。低剂量TGP显著降低了高尿酸血症大鼠血清中的MDA水平（P<0.05）和尿酸水平（P<0.01），升高了SOD（P<0.01）水平。高剂量TGP显著降低了高尿酸血症大鼠血清中的ALT（P<0.05）、尿酸（P<0.01）和XOD水平（P<0.05），升高了SOD水平（P<0.01）；病理观察发现，高剂量TGP能缓解高尿酸血症大鼠肝细胞脂肪变性、肝细胞周围纤维化和尿酸盐结晶沉积。结论：TGP能显著改善高尿酸血症大鼠肝细胞的氧化损伤和肝脏病理损伤，从而对高尿酸血症并发肝脏损伤有一定的保护作用。
- 高尿酸血症 /
- 白芍总苷 /
- 肝脏 /
- 黄嘌呤氧化酶 /
- 病理
Abstract: Objects: To investigate the protective effect of total glucosides of peony (TGP) on rats with hyperuricemia and liver damage. Methods: Fifty male Sprague-Dawley rats were randomLy divided into 5 groups: The normal group, the model group, the TGP low dose group (100 mg/kg), the TGP high dose group (300 mg/kg) and the allopurinol group (27.0 mg/kg), with 10 rats in each group. The hyperuricemia rat model was established by gavage of adenine 6.66 mg/mL+oteracil potassium 100 mg/mL suspension (1.5 mL/100 g) in the model group, TGP low dose group, TGP high dose group and allopurinol group respectively, once respectively of 7:00 and 20:00, continues for 3 weeks. TGP and allopurinol were intragastrically administered at 12:00 every day, and continues for 5 weeks. After 5 weeks, the rats were sacrificed. The liver organ index was measured, the content of serum total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), superoxide dismutase (SOD), uric acid and xanthine oxidase (XOD) were measured, and the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) in serum were measured. At the same time, pathological changes of the liver were observed. Results: Both the high and low doses of TGP significantly increased the liver organ index of hyperuricemia rats (P<0.01). Low dose TGP decreased the level of MDA (P<0.05) and significantly decreased the level of uric acid (P<0.01), significantly increased the levels of SOD (P<0.01) in serum of hyperuricemia model rats. High dose TGP decreased the levels of ALT (P<0.05) and XOD (P<0.05), significantly decreased the level of uric acid （P<0.01）, significantly increased the level of SOD (P<0.01) in serum of hyperuricemia model rats. Pathological observation showed that high dose TGP alleviated hepatocyte steatosis, perihepatocyte fibrosis and urate crystal deposition in hyperuricemia rats. Conclusion: TGP would have a good hepatic protective effect during hyperuricemia through significantly improveing the oxidative damage and liver pathological damage of hepatocytes in hyperuricemia rats.
- hyperuricemia /
- total glucosides of peony /
- liver /
- xanthine oxidase /
- pathology

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图 1 各组大鼠肝脏HE染色病理变化（400×）

Figure 1. Pathological changes of liver in rats of each group observed by HE staining (400×)

注：黑色箭头：肝小叶中央静脉充血；蓝色箭头：肝细胞脂肪变性。a：正常组；b：模型组；c：TGP低剂量组；d：TGP高剂量组；e：别嘌醇组；图2、图3同。

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图 2 各组大鼠肝脏Masson染色病理变化（400×）

Figure 2. Pathological changes of liver in rats of each group observed by Masson staining (400×)

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图 3 各组大鼠肝脏尿酸盐结晶沉积情况（Gomori六胺银染色，400×）

Figure 3. Urate crystal deposition in liver of rats in each group (GMS, 400×)

注：黑色箭头：尿酸盐结晶; $ {\rm{\overline x}} \pm {\text{s}}$，n=10。

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表 1 各组大鼠体重及肝脏脏器指数变化情况

Table 1. Changes of body weight and liver index of rats in each group

组别	体重（g）	肝脏脏器指数（%）
正常组	407.17±11.18	2.98±0.19
模型组	343.00±14.98^**	2.96±0.37
TGP低剂量组	341.60±14.24^**	3.82±0.36^**##
TGP高剂量组	369.25±44.61^*	3.74±0.35^**##
别嘌醇组	346.67±24.23^**	3.22±0.33
注：与正常组相比，^P<0.05，^*P<0.01；与模型组相比，^#P<0.05，^##P<0.01，表2~表5、图3同。

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表 2 各组大鼠血清中尿酸和XOD水平的变化情况

Table 2. Changes of serum uric acid and XOD levels in rats in each group

组别	尿酸（μmol/L）	XOD（U/L）
正常组	74.54±27.07	25.33±2.65
模型组	166.67±36.18^**	39.01±5.57^**
TGP低剂量组	132.84±34.31^**##	35.02±6.45^*
TGP高剂量组	112.75±12.98^**##	29.74±8.10^#
别嘌醇组	113.29±8.69^**##	25.81±4.06^##

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表 3 各组大鼠血清中AST和ALT水平的变化情况

Table 3. Changes of serum AST and ALT levels in rats in each group

组别	AST（U/L）	ALT（U/L）
正常组	55.33±3.52	21.47±4.05
模型组	61.04±5.35^**	30.87±6.17^**
TGP低剂量组	59.08±5.20^*	29.08±6.17^**
TGP高剂量组	58.00±4.28	27.20±4.41^**#
别嘌醇组	55.83±4.47^##	28.33±4.03^**

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表 4 各组大鼠血清TC和TG水平的变化情况

Table 4. Changes of serum TC and TG levels of rats in each group

组别	TC（mmol/L）	TG（mmol/L）
正常组	1.92±0.63	1.51±0.40
模型组	1.26±0.27^**	0.58±0.15^**
TGP低剂量组	1.32±0.39^**	0.71±0.29^**
TGP高剂量组	1.49±0.24^**	0.75±0.09^**
别嘌醇组	1.49±0.34^**	0.82±0.32^**#

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表 5 各组大鼠血清MDA和SOD水平的变化情况

Table 5. Changes of serum MDA and SOD levels of rats in each group

组别	MDA（nmol/mL）	SOD（U/mL）
正常组	3.81±0.57	88.63±9.04
模型组	6.83±1.25^**	69.92±2.75^**
TGP低剂量组	5.21±0.91^*#	88.78±10.59^##
TGP高剂量组	5.78±0.59^**	89.90±8.10^##
别嘌醇组	5.90±1.12^**	90.28±11.05^##

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