卒中后抑郁患者小脑影像遗传学改变及电针的干预作用

The pathogenesis of post-stroke depression (PSD) remains unclear. Supported by the Nation Natural Science Foundation of China, we preliminarily confirmed that the cerebellum of PSD rats suffered from obvious alternations in animal experiments and that depressive symptoms of PSD rats could be improved by electric stimulation of cerebellar fastigial nucleus. However,We found that the cerebellum in some stroke rats with lesions of degree and location similar to PSD rats, remained undamaged. However,till now, the mechanism of selective damage of cerebellum after stroke is still unknown. Clinically, we found by magnetic resonance imaging (MRI) that the volumes of cerebellum of patients with PSD decreased obviously and the genotypic proportion of BDNF Val66 V/M in blood were increased than that of the control group.Therefore,we presumed that the involvement of cerebellar lesion after stroke is related to genetic susceptibility.Thus,the research will analysis quantitatively the alterations of the cerebellar structure and function and the correlation between these changes and depression scale scoring by imaging technology such as multisequencing MRI and PET. Then，we study the genetic basis of the cerebellar lesion,that is,to confirm the relevance between the cerebellar lesion and the polymorphism of Brain-Derived Neurotrophic Factor (BDNF) and glucocorticoid receptors (GR). Meanwile,we study the mechanism of protective effect of electroacupuncture on cerebellum. At last, our final aim is to prove the hypotheses that based on genetic susceptibility, the damaged cerebellum, secondary to the stroke, results in PSD. And the mechanism of improving depression syndrome by electroacupuncture at Wangu acupoint is through alleviating damage of the cerebellum. We are convinced that the study may help to further clarify the pathogenesis of PSD and undoubtedly open up a new therapeutic trend for PSD.

卒中后抑郁（PSD）发病机制至今不清。前期我们在国家自然科学基金资助下的动物实验证实PSD大鼠小脑结构与功能发生了明显改变，电针小脑顶核改善了抑郁。但实验中发现,在卒中部位及程度均相似的大鼠中，部分大鼠小脑并未损伤，目前小脑的选择性损伤机制不明。前期我们通过MRI发现PSD患者小脑体积减小而血中BDNF Val66 V/M基因型频率高于对照组，故我们推测卒中后小脑损伤的发生与遗传易感性有关。故本课题将利用多序列MRI及PET影像技术定量研究PSD患者小脑形态及功能变化并分析其与抑郁量表评分间的相关性；在此基础上进一步研究小脑损伤的遗传学基础，即其与BDNF和糖皮质激素受体基因多态的关联性；同时研究电针改善抑郁的小脑保护机制，从而证实我们的假说,即在遗传易感基础上，卒中继发的小脑损伤导致了PSD的发生,而电针通过减轻其损伤缓解抑郁。本研究将为进一步阐明PSD发病机制，进而为其防治开辟新方向。

卒中后抑郁（PSD）发病机制仍不明。前期我们在国家自然科学基金资助下的动物实验证实PSD大鼠小脑结构与功能发生了明显改变。临床发现PSD患者小脑血流明显下降，电针完骨穴（对应小脑顶核）明显改善了抑郁症状，但相似的卒中患者并非必然发生PSD。故本课题将利用影像遗传学方法研究PSD患者小脑形态功能的改变及电针的保护机制：①利用多序列MRI及PET等影像技术定量分析PSD患者小脑形态及功能的变化并分析这些变化与抑郁量表评分间的相关性；②研究BDNF和糖皮质激素受体基因多态与小脑损伤的关联性；③研究电针完骨穴改善抑郁的小脑保护机制。研究对象分为3组，分别为卒中后抑郁组（PSD组），卒中后无抑郁组（CONT组）及对照组（NORM组）。PSD组患者小脑后叶下部的体积和小脑中、下脚的FA值较CONT组及NORM组均有显著降低(P＜0.05)；CONT组与健康对照组小脑各部分的体积和FA值比较无统计学差异（P＞0.05）；PSD组患者小脑后叶下部的体积减小与HAMD评分成显著负相关，相关系数为-0.896，P＜0.05；同样，PSD组患者小脑中、下脚FA值的降低与HAMD评分均成显著负相关，相关系数分别为-0.704和-0.916，均P＜0.05。CONT组双侧小脑NAA/Cr、Cho/Cr、Cho/NAA比值分别与NORM组比较，差异无统计学意义（P>0.05）。PSD组病灶对侧小脑Cho/Cr、Cho/NAA比值均高于NORM组和CONT组，差异均有统计学意义(P<0.05)，病灶同侧小脑Cho/Cr、Cho/NAA比值分别与NORM组和CONT组相比，差异无统计学意义（P>0.05），而双侧小脑NAA/Cr比值与NORM组和CONT组相比，差异无统计学意义（P>0.05）。家庭APGAR问卷评分、ARWMC评分、发病14天时NIHSS评分、病灶对侧小脑Cho/Cr和Cho/NAA比值与卒中后抑郁有关。多重线性回归分析显示病灶对侧小脑Cho/Cr、Cho/NAA比值与HAMD评分具有相关性（P<0.05）。PSD患者小脑形态结构发生了改变且这种改变与抑郁状态呈显著相关性，进而从临床上初步证实了小脑可能参与了卒中后抑郁的发生。