二苯乙烯苷对脑缺血再灌注大鼠TrkA及Bcl-2表达的影响

目的探讨二苯乙烯苷（TSG）对脑缺血再灌注大鼠的神经保护作用及机制。方法将250～350g健康雄性sD大鼠共4组：对照组、模型组、小剂量TSG组和大剂量TSG组，每组24只。Longa线栓法制备大脑中动脉栓塞模型（MCAO），按Longa的5级标准评分法评价神经功能缺损。再灌注后6h、24h、48h和7d共4个时间点处死大鼠。采用原位末端脱氧核苷酸转移酶标记法（TUNEL）检测神经细胞凋亡；采用原位杂交方法、免疫组化法检测TrkA、Bcl-2基因／蛋白表达变化。结果神经功能缺损评分显示造模各组各时间点均有明显的神经功能缺损症状，除6h时间点外，两个剂量TSG治疗组其余各时间点神经功能缺损评分明显低于模型组，差异有统计学意义（P〈0．05）；与模型组比较，两个剂量TSG组各时间点凋亡细胞减少，TrkA、Bcl-2基因／蛋白的表达明显上调，差异都有统计学意义（P〈0．05）。结论TSG可能通过增强脑缺血再灌注损伤后TrkA／Bcl-2通路的活性，起到神经保护作用。

Effects of tetrahydroxystilhene glucoside on expression of TrkA and Bcl-2 in rats after cere- bral ischemia/reperfusion

Objective To investigate the neuroprotective effect＇of tetrahydroxystilhene glucoside （TSG）, an effective component of Polygonum multiflorum thunb. , in rats after cerebral ischemia/reperfusion （I/R） and its action mechanism. Methods Healthy male Sprague-Dawley rats weighting 250 - 350 g were divided into control, model, low-dose TSG （60 mg/kg/d） , and high-dose TSC （ 120 mg/kg/d） groups, 24 each. A rat model of middle cerebral artery occlusion was established by Longa＇ s method, and the neurological behavior was evaluated by Longa＇ s scoring. Rats were sacrificed at 6 hrs, 24 hrs, 48 hrs, and 7 days after reperfusion in the cerebral cortex, and the apoptosis of nerve cells was detected by terminal deoxynucleotidyl transferase-mediated nick-end labe- ling. Meanwhile, the mRNA and protein expression of TrkA and Bcl-2 was measured by in situ hybridization and immunohistochem- istry, respectively. Results All rats treated by I/R showed marked neurological deficit symptoms at all time points after reperfusion. Compared with the model group, the two TSG groups had significantly lower neurological deficit scores at 24 hrs, 48 hrs, and 7 days after reperfusion （ P 〈 0.05 ） , as well as significantly reduced numbers of apoptotic cells and significantly increased mRNA and pro- tein expression of TrkA and Bcl-2 at all time points after reperfusion （P 〈 0.05 for both）. Conclusions TSG improves the neurolog- ical function and reduces the number of apoptotic cells in rats after cerebral I/R, probably by increasing the expression of TrkA and Bcl-2.