三碘甲状腺原氨酸促进2VO大鼠侧脑室下区的神经再生

目的：探讨三碘甲状腺原氨酸（triiodothyronine，T3）对双侧颈总动脉结扎（2-vessel occlusion，2VO）大鼠侧脑室下区（subventri（sular zone．svz）神经再生的影响。方法：雄性SD大鼠完全随机分为假手术组，2VO组和缺血后T3干预组，每组8只，采用双侧颈总动脉永久性结扎术制备慢性脑缺血模型，术后各组大鼠连续7d腹腔注射5-溴脱氧尿嘧啶核苷（5-Bromo-2′-deoxyuridine，BrdU）标记增殖细胞。各组5只分别于第7、14天灌注取脑组织，采用BrdU与Doublecortin（DCX）免疫荧光双染法标记新生神经元；各组3只取新鲜脑组织分离SVZ，采用免疫印迹法检测DCX蛋白的表达水平。结果：T3作用7d后，T3干预组BrdU阳性细胞较假手术组显著增多（P=0．002），与2VO组差异无统计学意义（P=0．084）；且BrdU／DCX阳性细胞较2VO组和假手术组均显著增多（均P〈0．05）。T3作用14d后，T3干预组BrdU阳性细胞和BrdU／DCX阳性细胞均显著多于2VO组和假手术组（P〈0．01）。与2VO7d组相比，2VO14d组BrdU阳性细胞和BrdU／DCX阳性细胞显著减少（P〈0．05）。免疫印迹法也显示T3组DCX蛋白的表达水平较多、结论：T3可促进慢性脑缺血大鼠侧脑室下区新生神经元的增殖，提高存活率，促进神经再生。

Triiodothyronine promotes neurogenesis in subventricular zone in 2VO rats

Objective：To investigate the effects of triiodothyronine on neurogenesis in the subventricular zone following bilateral common carotid artery occlusion （2VO） in rats. Methods： Male Sprague-Dawlcy （SD） rats were ramlomly assigned to sham （n = 8）, 2VO （n = 8） and 2VO ＋ T3 intervention group （n = 8）. Permanent bilateral common carotid artery occlusion was performed to establish a chronic cerebral hypopcffusion model. This was followed by 5-bromo-2′-deoxyuridine （BrdU） intraperitoneal injection for 7 days to label the proliferating cells. Five rats in each group were sacrificed at days 7 and 14 to extract the cerebral tissues for subsequent fluorescent immunostaining with BrdU and doublecortin （DCX） to label neurogenesis, and the remaining 3 rats were sacrificed for extraction of SVZ from cerebral tissues to assay the expression of DCX via immunoblotting. Results ： At day 7 following administration of T3 , the T3 intervention group yielded substantially increased BrdU-positive cells than sham group （ P = 0. 002）, but not 2VO group （ P = 0. 084）, as well as significantly increased BrdU/DCX-positive cells compared with 2VO and sham group （ both P 〈 O. 05 ）. At day 14 following administration of T3, a markedly higher BrdU- and BrdU-/DCX-positive cell count was found in T3 intervention group compared with 2VO and sham group （ both P 〈0.01 ）. Compared with day 7, the 2VO group had a considerably reduced number of BrdU- and BrdU-/DCX-positive cells at day 14 （P 〈 0.05 ）. Augmented expression of DCX, as evidenced by immunoblotting, was revealed in T3 intervention group. Conclusion： T3 may promote proliferation, survival and regeneration of neurons in the subventricular zone in 2VO rats.