抗精神病药对大鼠体内维生素D代谢的影响研究
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摘要
目的研究抗精神病药对大鼠体内维生素D代谢的影响。方法 SD大鼠随机分为5组:对照组、氟哌啶醇组、氯氮平组、利培酮组及阿立哌唑组,给药30 d后,测定大鼠血清25(OH)D、1,25(OH)2 D水平,CYP27B1与CYP24A1 mRNA表达及钙、磷浓度。结果抗精神病药干预30 d后,大鼠血清25(OH)D、1,25(OH)2 D水平及肾脏VD代谢酶CYP27B1与CYP24A1 mRNA相对表达相比对照组差异无统计学意义。结论相对较短周期的抗精神病药治疗并不引起体内维生素D代谢的显著变化,表明精神分裂症患者体内较低VD水平可能与服用抗精神病药无关。
Objective To investigate the impact of antipsychotic drug(APD) on vitamin D(VD) metabolism. MethodsSprague-Dawley rats were randomly divided into 5 groups and were given vehicle(n = 7), haloperidol [1 mg/(kg·d)], clozapine [20 mg/(kg·d)], risperidone [1 mg/(kg·d)] or aripiprazole [2 mg/(kg·d)] respectively. The serum level s of 25(OH) D and 1,25(OH)2 D were determined by a commercial enzyme-linked immunosorbent assay(ELISA), the mRNA levels of CYP27B1 and CYP24A1 in the kidney were measured by real-time PCR, and the concentrations of calcium and phosphorus were analyzed after 30-day administration. Results Signifi cant changes of level of 25(OH) D, 1,25(OH)2 D in the serum and expression of CYP27B1 and CYP24A1 in the kidney were not observed in the SD rats after APD administration. Conclusion A relatively short period of antipsychotic treatment may not be able to affect VD metabolism, which further indicates that APD treatment might not contribute to the VD defi ciency in patients with schizophrenia.
Objective To investigate the impact of antipsychotic drug(APD) on vitamin D(VD) metabolism. MethodsSprague-Dawley rats were randomly divided into 5 groups and were given vehicle(n = 7), haloperidol [1 mg/(kg·d)], clozapine [20 mg/(kg·d)], risperidone [1 mg/(kg·d)] or aripiprazole [2 mg/(kg·d)] respectively. The serum level s of 25(OH) D and 1,25(OH)2 D were determined by a commercial enzyme-linked immunosorbent assay(ELISA), the mRNA levels of CYP27B1 and CYP24A1 in the kidney were measured by real-time PCR, and the concentrations of calcium and phosphorus were analyzed after 30-day administration. Results Signifi cant changes of level of 25(OH) D, 1,25(OH)2 D in the serum and expression of CYP27B1 and CYP24A1 in the kidney were not observed in the SD rats after APD administration. Conclusion A relatively short period of antipsychotic treatment may not be able to affect VD metabolism, which further indicates that APD treatment might not contribute to the VD defi ciency in patients with schizophrenia.
引文
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[11]K a p u r S,Va n d e r S p e k S C,B r o w n l e e B A,e t a l.Antipsy chotic dosing in preclinical models is often unrepresentative of the clinical condition:a suggested solution based on in vivo occupancy[J].J Pharmaco Exp Ther,2003,305(2):625-631.
[12]Jiang P,Zhang WY,Li HD,et al.Repeated haloperidol administration has no effect on vit amin D signaling but increase retinoid X receptors and Nur77 expression in rat prefrontal cortex[J].Cell Mol Neurobiol,2013,33(3):309-312.
[13]Costa JL,Smith G,Watson M,et al.The atypical antipsy chotic clozapine decreases bone mass in rats in vivo[J].Schizophr Res,2011,126(1-3):291-297.
[14]de Waal EJ,Roosen W,Vinken P,et al.Mechanistic investigations on the etiology of Risperdal Consta-induced bone changes in female Wistar Hannover rats[J].Toxicology,2012,299(2-3):90-98.
[15]李晓一,陈虹,陈杏丽,等.利培酮治疗首发精神分裂症患者1年骨密度变化的病例对照研究[J].上海精神医学,2011,23(5):278-283.
[16]Crews M,Lally J,Gardner-Sood P,et al.Vitamin D defi ciency in fi rst episode psychosis:a case-control study[J].Schizophr Res,2013,150(2-3):533-537.
[17]Wyszogrodzka-Kucharska A,Rabe-Jab?ońska J.Calcium balance and regulation in schizophrenic patients treated with second generation antipsychotics[J].Psych iatr Pol,2005,39(6):1157-1171.
[2]Kishimoto T,De Hert M,Carlson HE,et al.Osteoporosis and fracture risk in people with schizophrenia[J].Curr Opin Psychiatry,2012,25(5):415-429.
[3]Kishimoto T,Watanabe K,Takeuchi H,et al.Bone mineral density measurement in female inpatients with schizophrenia[J].Schizophr Res,2005,77(1):113-115.
[4]Agorastos A,Weinas A,Agorastos AD,et al.Psychosisinduced vitamin D deficiency with secondary hyperparathyroidism and osteoporotic fractures[J].Gen Hosp Psychiatry,2011,33(6):641-645.
[5]McGrath JJ,Burne TH,Féron F,et al.Developmental vitamin D deficiency and risk of schizophrenia:a 10-year update[J].Schizophr Bull,2010,36(6):1073-1078.
[6]付强,刘源.钙、磷与维生素D对动物骨代谢的影响研究进展[J].中国比较医学杂志,2006,16(8):502-505.
[7]Crews MP,Howes OD.Is antipsychotic treatment linked to low bone mineral density and osteoporosis?A review of the evidence and the clinical implications[J].Hum Psychopharmacol,2012,27(1):15-23.
[8]Howes OD,Wheeler MJ,Meaney AM,et al.Bone mineral density and its relationship to prolactin levels in patie nts taking antipsychotic treatment[J].J Clin Psychopharmacol,2005,25(3):259-261.
[9]Lee TY,Chung MY,Chung HK,et al.Bone density in chronic schizophrenia with long-term antipsychotic treatment:preliminary study[J].Psychiat Invest,2010,7(4):278-284.
[10]Wadenberg ML,Soliman A,VanderSpek SC,et al.Dopamine D(2)receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects[J].Neuropsychopharmacology,2001,25(5):633-641.
[11]K a p u r S,Va n d e r S p e k S C,B r o w n l e e B A,e t a l.Antipsy chotic dosing in preclinical models is often unrepresentative of the clinical condition:a suggested solution based on in vivo occupancy[J].J Pharmaco Exp Ther,2003,305(2):625-631.
[12]Jiang P,Zhang WY,Li HD,et al.Repeated haloperidol administration has no effect on vit amin D signaling but increase retinoid X receptors and Nur77 expression in rat prefrontal cortex[J].Cell Mol Neurobiol,2013,33(3):309-312.
[13]Costa JL,Smith G,Watson M,et al.The atypical antipsy chotic clozapine decreases bone mass in rats in vivo[J].Schizophr Res,2011,126(1-3):291-297.
[14]de Waal EJ,Roosen W,Vinken P,et al.Mechanistic investigations on the etiology of Risperdal Consta-induced bone changes in female Wistar Hannover rats[J].Toxicology,2012,299(2-3):90-98.
[15]李晓一,陈虹,陈杏丽,等.利培酮治疗首发精神分裂症患者1年骨密度变化的病例对照研究[J].上海精神医学,2011,23(5):278-283.
[16]Crews M,Lally J,Gardner-Sood P,et al.Vitamin D defi ciency in fi rst episode psychosis:a case-control study[J].Schizophr Res,2013,150(2-3):533-537.
[17]Wyszogrodzka-Kucharska A,Rabe-Jab?ońska J.Calcium balance and regulation in schizophrenic patients treated with second generation antipsychotics[J].Psych iatr Pol,2005,39(6):1157-1171.