维生素D对Tourette综合征模型大鼠运动功能和刻板行为的影响

Effects of vitamin D on locomotor function and stereotyped behaviors of Tourette syndrome model rats

目的观察维生素D(Vitamin D,VD)对Tourette综合征(Tourette syndrome,TS)模型大鼠运动功能及刻板行为的影响。方法 50只清洁级雄性SD大鼠按照随机数字表法分为正常对照组、TS模型对照组、TS模型+不同剂量VD干预组(TS模型+1.0 μg VD组、TS模型+0.6 μg VD组、TS模型+0.3 μg VD组),每组10只。采用腹腔注射亚氨基二丙腈(iminodipropionitrile,IDPN)的方法建立TS大鼠动物模型。由两人采取双盲法观察不同组别大鼠运动行为及刻板行为,并通过ELISA法及组织Von kossa染色检测大鼠血清钙离子、1,25-(OH)2-VD含量及肾脏钙离子沉积情况。采用SPSS 25.0统计软件对数据进行统计分析。结果造模成功后1~7 d及14 d,TS模型+1.0 μg VD组大鼠运动行为评分[1 d(0.69±0.29)分,2 d(0.63±0.34)分,3 d(0.65±0.24)分,4 d(0.52±0.43)分,5 d(0.53±0.35)分,6 d(0.43±0.43)分,7 d(0.53±0.34)分,14 d(0.58±0.55)分]及刻板行为评分[1 d(1.77±0.89)分,2 d (2.25±1.00)分,3 d(2.27±1.19)分,4 d(2.05±1.01)分,5 d(2.27±1.21)分,6 d(2.13±0.86)分,7 d(2.22±1.28)分,14 d(2.22±1.26)分]均低于TS模型对照组[运动行为评分:1 d(1.13±0.57)分,2 d(1.02±0.32)分,3 d(1.33±0.39)分,4 d(1.05±0.49)分,5 d(1.07±0.26)分,6 d(0.92±0.45)分,7 d(1.10±0.33)分,14 d(1.02±0.64)分;刻板行为评分:1 d(3.15±0.85)分,2 d(3.05±1.12)分,3 d(3.17±0.67)分,4 d(3.05±0.81)分,5 d(2.95±0.93)分,6 d(3.12±0.81)分,7 d(2.93±0.43)分,14 d(3.03±0.57)分],均差异具有统计学意义(均P<0.05)。TS模型+0.6 μg VD组大鼠运动行为评分[1 d(0.90±0.28)分,2 d(0.90±0.26)分,3 d(0.80±0.23)分,4 d(0.81±0.37)分,5 d (0.67±0.26)分,6 d(0.72±0.31)分,7 d(0.63±0.50)分,14 d (0.85±0.45)分]低于TS模型对照组,均差异具有统计学意义(均P<0.05)。TS模型+0.3 μg VD组大鼠运动行为评分及刻板行为评分与TS模型对照组评分差异均无统计学意义(均P>0.05)。TS模型+1.0 μg VD组大鼠血清钙离子含量[(3.19±0.31)mmol/L]明显高于其余4组[正常对照组:(2.54±0.16)mmol/L,TS模型+0.6 μg VD组:(2.68±0.20)mmol/L,TS模型+0.3 μg VD组:(2.52±0.16)mmol/L,TS模型对照组:(2.62±0.21)mmol/L],差异具有统计学意义(均P<0.05),TS模型+1.0 μg VD组5只中2只大鼠出现肾脏散在钙化灶。结论 VD可以改善TS模型大鼠的运动行为及刻板行为,且呈剂量依赖性。

Objective To investigate the effects of vitamin D(VD)on locomotor behaviors and stereotyped behaviors of Tourette syndrome(TS)model rats.Methods Fifty SD rats were divided into normal control group,TS model control group,TS model+1.0μg VD group,TS model+0.6μg VD group and TS model+0.3μgVD group according to the random number table,and 10 rats in each group.The animal model of TS was established by intraperitoneal injection of iminodipropionitrile(IDPN).To observe the locomotor behaviors and stereotyped behaviors of different groups'rats by two independent blind observers.Serum calcium content and 1,25-(OH)2-VD were measured by Enzyme-linked immunosorbent assay and renal calcium deposition of rats by tissue Von Kossa staining.SPSS 25.0 was used to analyze the data.Results 1-7 days and 14 days after successful modeling,TS model+1.0μg VD group exhibited significantly decreased locomotor behaviors scores(1 d(0.69±0.29),2 d(0.63±0.34),3 d(0.65±0.24),4 d(0.52±0.43),5 d(0.53±0.35),6 d(0.43±0.43),7 d(0.53±0.34),14 d(0.58±0.55))and stereotypic behaviors scores(1 d(1.77±0.89),2 d(2.25±1.00),3 d(2.27±1.19),4 d(2.05±1.01),5 d(2.27±1.21),6 d(2.13±0.86),7 d(2.22±1.28),14d(2.22±1.26))compared with TS model control group(locomotor behaviors scores:1d(1.13±0.57),2 d(1.02±0.32),3 d(1.33±0.39),4 d(1.05±0.49),5 d(1.07±0.26),6 d(0.92±0.45),7 d(1.10±0.33),14 d(1.02±0.64);stereotyped behaviors scores:1 d(3.15±0.85),2 d(3.05±1.12),3 d(3.17±0.67),4 d(3.05±0.81),5 d(2.95±0.93),6 d(3.12±0.81),7 d(2.93±0.43),14 d(3.03±0.57),and the difference were statistically significant(all P<0.05).The scores of locomotor behaviors(1 d(0.90±0.28),2 d(0.90±0.26),3 d(0.80±0.23),4 d(0.81±0.37),5 d(0.67±0.26),6 d(0.72±0.31),7 d(0.63±0.50),14 d(0.85±0.45))of TS model+0.6μg VD group were lower than those in the TS model control group,and the differences were statistically significant(all P<0.05).There were no statistically significant differences in the scores of locomotor behaviors and stereotyped behaviors between the TS model+0.3μg VD group and TS model control group(both P>0.05).The serum calcium content of TS model+1.0μgVD group(3.19±0.31)mmol/L)were significantly higher than those of the other 4 groups(normal control group:(2.54±0.16)mmol/L,TS model+0.6μg VD group:(2.68±0.20)mmol/L,TS model+0.3μgVD group:(2.52±0.16)mmol/L,TS model control group:(2.62±0.21)mmol/L)(all P<0.05).In TS model+1.0μg VD group,2 rats in 5 had scattered calcification in the kidney.Conclusion VD can reduce the locomotor behaviors and stereotyped behaviors of TS model rats,which is dose-dependent.