缬沙坦对MPTP所致帕金森病模型小鼠的保护作用  

Protective effect of valsartan on the MPTP-induced mouse model of Parkinson's disease

作　　者：翁凤妹 王妍 唐正虎 黄伊俐 

机构地区：[1]解放军第四五八医院药剂科 [2]解放军75260部队卫生队 [3]广州军区广州疗养院疗养一科

出　　处：《中南药学》2016年第1期16-19,共4页Central South Pharmacy

摘　　要：目的研究降血压药物缬沙坦对帕金森病(PD)小鼠模型的大脑保护作用。方法 36只C57BL/6小鼠随机分成对照组、缬沙坦组、PD模型组、PD+缬沙坦组,每组9只。采用腹腔注射MPTP溶液建立PD小鼠模型;PD+缬沙坦组、缬沙坦组小鼠同时给予1 mg/(kg·d)缬沙坦每日灌胃,其余2组给予等体积生理盐水灌胃,实验周期为3周。神经功能评定采用爬杆实验和自主活动实验;免疫组化染色检测黑质区酪氨酸羟化酶阳性细胞数目;Western blot检测黑质部位α-共核蛋白、NF-κB蛋白表达。结果缬沙坦对各组实验小鼠血压无明显影响;与对照组比较,PD模型组和PD+缬沙坦组小鼠自主活动次数、黑质区酪氨酸羟化酶阳性细胞数目明显减少,爬杆时间明显延长、α-共核蛋白、NF-κB蛋白表达水平显著上升,差异比较均具有统计学意义(P<0.05);但与PD模型组比较,PD+缬沙坦组小鼠经缬沙坦干预后,自主活动次数、酪氨酸羟化酶阳性细胞数目增加,爬杆时间显著缩短,α-共核蛋白、NF-κB蛋白表达下调,差异比较均具有统计学意义(P<0.05)。结论缬沙坦可通过提高动物行为学功能、抑制黑质区酪氨酸羟化酶阳性细胞凋亡和下调α-共核蛋白、NF-κB蛋白表达而改善PD模型动物的神经功能。Objective To determine the cerebral protective effect ofvalsartan on the mouse model ot Parkmson＇s disease （PD）. Methods Thirty-six C57BL/6 mice were chosen and equally, randomized into a control group, a valsartan group, a PD model group, and a PD ＋ valsartan group. The number of mice in each group was 9. MPTP was given for 8 days to the mice in the PD model group and PD ＋ valsartan group intraperitoneally; mice in the PD ＋ valsartan group and the valsartan group were orally administered valsartan for 3 weeks. Neurologi- cal behaviors were measured through pole test and spontaneous movement test; tyrosine hydroxylase （TH） im- munoreactivity in the substantia nigra pars compacta （SNc） was observed. Protein level of α-synuclein, NF-κB were determined by Western blot. Results Valsartan had no effects on the blood pressure in the mice. Compared with the control group, the behavior and number of TH positive cells in the mice were markedly decreased （all P 〈 0.05）; the protein expression levels of α-synuclein, and NF-κB were significantly increased （all P 〈 0.05）. After the 3 weeks valsartan intervention, the animal behavior function and number of TH positive cells were markedly increased; the protein expression level of α-synuclein, NF-κB were significantly down regulated compared to the PD model group （all P 〈 0.05）. Conclusion Valsartan plays a neuroprotective role in MPTP-induced PD mice by improving animal behaviors, decreasing TH positive cell apoptosis and α-synuclein, NF-κB protein expression levels.

关 键 词：帕金森病 缬沙坦 酪氨酸羟化酶 核因子-ΚB Α-共核蛋白 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R285.1[医药卫生—临床医学]