尼莫地平对生长受限胎鼠大脑皮层钙离子通道表达的影响及意义

Effects and significance of nimodipine on the level of calcium channels in the cortex of growth restricted rat pups

目的探讨孕期应用钙离子拮抗剂尼莫地平对生长受限胎鼠脑组织钙离子通道表达及神经元凋亡的影响。方法SD孕鼠随机分为三组：（1）对照组，10只，于妊娠17d行假手术；（2）胎儿生长受限（fetal growth restriction，FGR）组，20只，于妊娠17d缩窄双侧子宫动脉；（3）治疗组：20只，建模同FGR组，术后予尼莫地平0．2mg／（kg·d）腹腔注射直至分娩。采用RT-PCR技术检测各组仔鼠大脑皮层P／Q型钙离子通道亚单位αlA、L型钙离子通道亚单位αlDmRNA水平；通过脱氧核糖核酸转移酶介导的X-dUTP缺口末端标记（terminal deoxynucleotide transferase X—dUTP nick end labeling，TUNEL）法检测各组新生仔鼠皮层神经元凋亡情况。结果（1）皮层αlAmRNA水平：对照组为0．464±0．062，明显低于FGR组（0．653±0．093，P〈0．01）及治疗组（0．628±0．103，P〈0．01），而FGR组和治疗组之间差异无统计学意义（P〉0．05）；αlDmRNA水平FGR组高于治疗组（分别为0．992±0．074和0．797±0．800，P〈0．01），治疗组高于对照组（0．712±0．097，P〈0．01）。（2）皮层神经元凋亡率：治疗组低于FGR组[分别为（2．98±0．54）个／高倍视野和（5．05±1．17）个／高倍视野，P〈0．01]，但高于对照组[（2．3±0．69）个／高倍视野，P〈0．01]。结论尼莫地平孕期干预能抑制FGR胎鼠大脑皮层钙离子通道亚单位αlDmRNA的水平，降低神经元凋亡率，对FGR胎鼠神经系统损伤可能有一定的保护作用。

Objective To study the effects of nimodipine treatment during pregnancy on the level of calcium channels and neuronal apoptosis in the cortex of growth restricted rat pus. Methods Pregnant SD rats were randomly divided into 3 groups. Sham operation was exerted for rats in the control group（n= 10）, while bilateral uterine arteries were partially ligated in FGR group （n= 20） and the treatment group （n= 20）. In the treatment group, 0. 2 mg/（kg · d） nimodipine was administrated subcutaneously after operation till delivery. The mRNA level of L type calcium channel （CaC） subunit αlD and P/Q type subunit αlA were measured by RT-PCR. Neuronal apoptosis in cortex was detected by terminal deoxynucleotid transferase X-dUTP nick end labeling （TUNEL）. Results The＇level of CaC αlA mRNA in cortex in the control group was 0. 464 ± 0. 062, lower than FGR group （0. 653 ± 0. 093, P〈0.01） and the treatment group （0. 628±0. 103,P〈0. 01）. There was no difference between the later two groups（P〈0. 05）. The level of CaC αlD mRNA in cortex in FGR group was higher than the treatment group （0. 992±0. 074 vs 0. 797±0. 800, P〈0. 01）, and the treatment group was higher than the control group （0. 712 ± 0. 097, P〈0.01）. The ratio of neuronal apoptosis in the cortex in the treatment group was lower than FGR group（2.98±0.54/HP vs 5.05±1.17/HP, P〈 0.01）, but higher than the control group（2.3±0.69/HP, P〈0.01）. Conclusions Nimodipine treatment during pregnancy could inhibit αlD gene transcription and decrease neuronal apoptosis ratio in cortex. So it may had neuroprotective effect on nervous system injuries induced by FGR.