电针调控慢性脑灌流不足大鼠海马神经发生的Noggin/BMP4机制研究

Noggin/BMP4 Mechanism of Electroacupuncture on Hippocampal Neurogenesis in Rats with Chronic Cerebral Hypoperfusion

目的观察电针通过调节Noggin/骨结合蛋白-4(BMP4)对慢性脑灌注不足大鼠海马神经发生的影响。方法使用双血管阻断法(2-VO)制作成年大鼠慢性脑灌注不足模型。采用B5-溴脱氧尿嘧啶核苷(BrdU)标记分裂细胞方法,观察和比较慢性脑缺血损伤后1周、2周、4周时电针组、模型组与假手术组海马齿状回神经干细胞的增殖、分化水平。结果 (1)电针对慢性脑灌注不足大鼠海马Noggin与BMP4基因表达的影响:与模型组同时间比较,电针组Noggin相对表达明显升高(P <0.05或P <0.01);与模型组同时间相比,电针组BMP4 mRNA有所降低(P <0.05)。(2)神经干细胞的增殖情况:电针组各时间大鼠海马齿状回颗粒下层的BrdU阳性细胞多于模型组。(3)神经干细胞分化情况:造模后2周,海马颗粒细胞层可见少量BrdU+NeuN及BrdU+GFAP双阳性表达细胞,造模后第4周双表达阳性细胞数明显增多;与4周模型组相比,电针组分化为神经元的比例较明显(P <0.05)。结论电针能够促进慢性脑灌注不足大鼠海马Noggin的表达,抑制BMP4的表达,促使海马神经干细胞的增殖,随治疗时间延长可诱导其向神经元分化;电针通过调节Noggin与BMP4的表达,促进神经干细胞增殖和定向分化可能是电针治疗慢性脑缺血疾病机制之一。

Objective To research the effect of electro acupuncture on hippocampal neurogenesis in rats with chronic cerebralhyoperfusion through regulating Noggin/BMP4.Methods Rats were induced into chronic cerebral hyoperfusion models by 2 -VO;5-bromodeoxyuridine （BrdU） was used to label dividing cells to observe and compare the multiplication and differentiation of neural stemcells in the dentate gyrus （DG）.All rats were divided into Electro acupuncture group,control groups （Model group and Sham operationgroup） at 1 week,2 weeks ,and 4 weeks after chronic cerebral hyoperfusion injury.Proliferation and differentiation levels of dentate gy -rus neural stem cells were observed.Results ①The hgfmrna of noggin in EA Groups was higher obviously than that in the ModelGroups at the same time;while BMP4 expression was lower significantly （P 〈0.05 or P 〈0.01）.②The proliferation of NSC：Comparedwith model group,the number of the BrdU positive cells in the hippocampal dentate gyrus EA group at same time was much more.③The differentiation of NSC：Two weeks after ischemia,a small amount of BrdU＋NeuN and BrdU＋GFAP positive cells expressed inhippocampal Granular cell layer （GCL）,and then these cells increased obviously after 4 weeks,with significant difference comparedwith the model group （P 〈0.05）.Conclusion Electro acupuncture could promote the expression of hippocampal Noggin gene andinhibit the expression of BMP4 in rats with chronic cerebral hyoperfusion,as well as improve the proliferation and differentiation ofNSC.It may be one of the mechanisms that electro acupuncture could treat chronic cerebral ischemia diseases by regulating the ex -pression of Noggin and BMP4 to improve proliferation and differentiation of the NSC.