Ghrelin 对MPTP小鼠帕金森病模型黑质THBcl2和Bax mRNA表达影响.docVIP

Ghrelin 对MPTP小鼠帕金森病模型黑质TH、Bcl2和Bax mRNA表达的影响 【摘要】 目的 探讨Ghrelin对1甲基4苯基1，2，3，6四氢吡啶（MPTP）造成的黑质（SN）多巴胺能神经元损伤的保护作用及可能机制。方法 小鼠随机分为对照组、MPTP组和Ghrelin+MPTP组。腹腔注射MPTP制备帕金森病小鼠模型；Ghrelin+MPTP组于MPTP注射前，侧脑室微量注射Ghrelin 200 ng，共8 d；对照组以等量生理盐水取代Ghrelin和MPTP。应用半定量RTPCR技术检测各组小鼠SN内酪氨酸羟化酶（TH）、Bcl2和Bax mRNA的表达情况。结果 MPTP导致小鼠SN内TH mRNA的表达明显低于对照组(F=34.77，q=11.91，Plt;0.01)，Ghrelin预处理小鼠SN内TH mRNA表达量较MPTP组明显增加(q=5.05, Plt;0.01)。MPTP导致小鼠SN内Bcl2/ Bax由对照组的1.13±0.03减少至0.47±0.06 (F=111.59，q=17.58,Plt;0.01)，Ghrelin预处理小鼠Bcl2/Bax明显高于MPTP组(q=18.94,Plt;0.01)，可恢复至正常水平。结论 Ghrelin预处理对于MPTP造成的TH基因表达量减少有改善作用，该作用可能通过抗凋亡途径实现。 【关键词】 Ghrelin 帕金森病 1甲基4苯基 四氢吡啶 酪氨酸单氧化酶 细胞凋亡 ［ABSTRACT］ObjectiveTo investigate the effect of Ghrlein on tyrosine hydroxylase (TH), Bcl2 and Bax mRNA expression of the subatantia nigra in 1methy4phenyl1,2,3,6tetrahydropyridine (MPTP)induced mouse model of Parkinson disease. MethodsEighteen healthy male C57BL/6 mice were divided into three groups at random：Control, MPTP and Ghrelin+MPTP. The mice in MPTP group were injected with MPTP (30 mg/kg, i.p.), once daily for five days, with Ghrelin (i.c.v.), 2 h before the injection of MPTP, once daily for eight days. As for the Control group, MPTP and ghrelin were replaced by normal saline. The total mRNA of the substantia nigra (SN) was collected to detect the mRNA expression of TH, Bcl2 and Bax by semiquantitive reverse transcription polymerase chain reaction. ResultsCompared with the control group, MPTP induced a reduction of TH mRNA expression (Plt;0.01). Pretreated with ghrelin showed an increase of TH mRNA expression compared with MPTP group (Plt;0.01). MPTP also decreased the ratio of Bcl2/Bax to 0.47±0.06 (Plt;0.01). And ghrelin could reverse the reduction induced by MPTP (Plt;0.01). ConclusionGhrelin could inhibit the reduction of TH mRNA expression induced by MPTP. The antiapoptotic pathway might be the mechanism of this neuroprotective effect. ［KEY WORDS］Ghrelin; Parkinson disease; 1methy4phenyl1,2,3,6t