维生素 U 对丙戊酸钠所致大鼠肾毒性的保护作用_癫痫杂志

2018, 4(6): 486-491. doi:10.7507/2096-0247.20180078

维生素 U 对丙戊酸钠所致大鼠肾毒性的保护作用

江娇美 , 陆晓妹 , 张明 , 赵晶 , 冷宇 , 吴鹏程 , 王芬

南昌大学第二附属医院神经内科（南昌 330006）

基金项目: 江西省教育厅科学技术研究（青年）基金（GJJ170157）

通讯作者: 赵晶, Email: 8734590@qq.com

Protective effects of vitamin U on valproic acid-induced renal damage in rats

JIANG Jiaomei , LU Xiaomei , ZHANG Ming , ZHAO Jing , LENG Yu , WU Pengcheng , WANG Fen

Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

Corresponding Author: ZHAO Jing, Email: 8734590@qq.com

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目的探讨维生素 U（Vit U）对丙戊酸钠（VPA）所致大鼠肾毒性的保护作用，为临床应用提供实验室依据。方法将 48 只雌性 SD 大鼠随机分为 4 组（n=12），对照组（A 组）、VitU 组（B 组）、VPA 组（C 组）、Vit U+VPA 组（D 组）。A 组：等量生理盐水；B 组：Vit U 50 mg/（kg·d）；C 组：VPA 300 mg/（kg·d）；D 组：先给予 Vit U 50 mg/（kg·d），1 h 后 VPA 300 mg/（kg·d）。连续给药 2、4 周后，分别采血后开腹取肾（n=6）。检测血清总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白 (HDL)、低密度脂蛋白 (LDL)、肌酐（Cr）、尿素氮（BUN）及尿酸（UA）的水平。结果 ① 血脂：2、4 周时与 A 组相比，C 组的 TC 及 LDL 均升高，差异具有统计学意义（P<0.05）；② 肾功能血清生化指标：2 周时与 A 组相比较，B、C、D 三组的 Cr、BUN 及 UA，差异均无统计学意义（P>0.05）；4 周时 C 组的 Cr、BUN 及 UA 水平与其他三组相比明显增高（P<0.05），差异具有统计学意义，D 组与 A 组相比较差异无统计学意义（P>0.05）；③ 肾组织损伤：2 周时各组肾脏组织形态学无明显异常，4 周时仅 C 组可见炎性病灶，余各组无明显异常。结论 VPA 可导致大鼠血脂水平升高，诱导的肾毒性可能与药物暴露时间有一定的关系；Vit U 对 VPA 所致大鼠的肾毒性具有一定的保护作用。

Objective The aim of present study was to investigate the protective effect of vitamin U on renal toxicity induced by sodium valproate (VPA) and provide laboratory data for clinical application of VPA. Methods In this study, 48 female rats were used. These animals were randomly divided into 4 groups: control group (group A), vitamin U group (group B), VPA group (group C), vitamin U+ VPA group (group D). Group A was given the same amount of normal saline, group B was given Vit U 50 mg/(kg·d), group C was given VPA 300 mg/(kg·d) and group D was given Vit U 50 mg/(kg·d) firstly, then VPA 300 mg/(kg·d) after 1 hours by gavage. After 2 or 4 weeks of continuous administration, the kidneys were collected from these rats after blood collection. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), serum creatinine (Cr), urea (BUN) and uric acid (UA) were detected by automatic biochemical analyzer. Result ① Blood lipid. There were significant differences in TC and LDL between the group A and group C (P<0.05), and the level of TC and LDL in group C were significantly higher. ② Serum biochemical indexes of renal function. There was no significant difference in Cr, UA and BUN four groups at 2w (P>0.05). At 4w, compared with the other three groups, the Cr, BUN and UA level of VPA group were significantly higher (P<0.05). But there was no significant difference between the group A and the group D. ③ Pathological morphology of renal tissue. At 2w, there was no obvious abnormality in renal structures among the four groups. At 4w, inflammatory lesions were only seen in VPA group, and mild inflammatory cell infiltration were seen in other three groups. Conclusion VPA can lead to a higher level of blood lipid. The renal toxicity induced by VPA may have a certain relationship with the time of drug exposure, and vitamin U has a protective effect on the renal toxicity induced by VPA.

关键词: 丙戊酸钠; 维生素 U; 肾功能; 大鼠

Key words: Valproic Acid; Vitamin U; Renal Function; Rat

引用本文： 江娇美, 陆晓妹, 张明, 赵晶, 冷宇, 吴鹏程, 王芬. 维生素 U 对丙戊酸钠所致大鼠肾毒性的保护作用. 癫痫杂志, 2018, 4(6): 486-491. doi: 10.7507/2096-0247.20180078 复制

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表1 各组大鼠血脂水平比较（，mmol/L)
Table1. The level of blood lipid in each group ( ，mmol/L)

组别 Group	只数 Number	总胆固醇 TC	甘油三酯 TG	高密度脂蛋白 HDL	低密度脂蛋白 LDL
2 周 2 Weeks
A 组	6	1.52±0.23	0.67±0.42	1.18±0.15	0.40±0.06
B 组	6	1.95±0.52	0.41±0.07	1.27±0.27	0.60±0.17
C 组	6	2.54±0.40^**	0.75±0.18^*	1.44±0.22	0.94±0.21^**
D 组	6	1.93±0.49^#	0.52±0.23	1.20±0.25	0.52±0.22^##
4 周 4 Weeks
A 组	6	1.57±0.12	0.31±0.03	0.47±0.02	0.28±0.04
B 组	5	1.63±0.47	0.38±0.13	0.48±0.13	0.30±0.17
C 组	6	1.99±0.27^*	0.30±0.05	0.53±0.05	0.40±0.08^*
D 组	6	1.60±0.28^#	0.29±0.08	0.50±0.04	0.29±0.07
注：TC 总胆固醇；TG 甘油三酯；HDL 高密度脂蛋白；LDL 低密度脂蛋白；^与 A 组相比 P<0.05；^与 A 组相比 P<0.01；^#与 C 组相比较 P<0.05；^##与 C 组相比较 P<0.01 Note：TC, total cholesterol; TG, triglyceride; HDL, high density lipoprotein; LDL, low density lipoprotein; ^ compared with group A, P<0.05;^** compared with group A, P<0.01;^# compared with group C, P<0.05;^## compared with group C, P<0.01

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表2 各组大鼠血清肌酐水平的比较（，μmol/L)
Table2. Comparison of serum creatinine levels in each group( , μmol/L)

组别 Group	只数 Number	2 周 2 Weeks	只数 Number	4 周 4 Weeks
A 组	6	34.76±5.22	6	40.37±0.85
B 组	6	31.91±4.39	5	40.43±4.47
C 组	6	32.87±4.95	6	58.67±5.55^**
D 组	6	37.57±6.17	6	41.79±6.33
t 值	−	0.64	−	−7.98
P 值	−	0.53	−	<0.01
注：^ 与 A 组相比 P<0.01 Note：^ compared with group A, P<0.01

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表3 各组大鼠血清尿素水平的比较（，mmol/L)
Table3. Comparison of serum urea levels in each group( , mmol/L)

组别 Group	只数 Number	2 周 2 Weeks	只数 Number	4 周 4 Weeks
A 组	6	7.92±0.84	6	7.79±0.91
B 组	6	7.97±0.23	5	6.76±0.33
C 组	6	7.97±1.19	6	10.34±1.13^**
D 组	6	7.60±1.46	6	7.87±1.39
t 值	−	−0.08	−	−4.33
P 值	−	0.93	−	<0.01
注：^ 与其他三组相比 P<0.01 Note：^ compared with other three groups, P<0.01

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表4 各组大鼠血清尿酸水平的比较（，μmol/L)
Table4. Comparison of serum uric acid levels in each group ( , μmol/L)

组别 Group	只数 Number	2 周 2 Weeks	只数 Number	4 周 4 Weeks
A 组	6	62.48±20.01	6	54.25±2.60
B 组	6	74.35±12.31	5	62.85±9.38
C 组	6	47.16±7.50	6	80.55±12.13^**
D 组	6	58.00±19.66	6	64.64±13.94
t 值	−	1.76	−	−5.19
P 值	−	0.11	−	<0.01
注：^ 与 A 组相比 P<0.01 Note：^ compared with group A, P<0.01

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图1 各组血清肌酐水平比较

Figure1. Comparison of serum creatinine level in each group

** compared with group A, P<0.01; ## compared with group C, P<0.01

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图2 各组血清尿素水平比较

Figure2. Comparison of serum urea level in each group

** compared with group A, P<0.01; ## compared with group C, P<0.01

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图3 各组血清尿酸水平比较

Figure3. Comparison of serum uric acid level in each group

** compared with group A, P<0.01; ## compared with group D, P<0.05

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图4 4 周时各组肾组织病理学改变

Figure4. The pathological chengas of renal tissue in each group at 4 week

The histopathological changes of kidneys in group A, B and D were normal at 4 week. There were obvious inflammatory lesions in group C（10×40）

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