四君子汤对FCIR大鼠大脑皮质神经保护作用的实验研究

目的：探讨四君子汤对局灶性脑缺血再灌注（focal cerebral ischemia-reperfusion，FCIR）大鼠大脑皮质神经保护作用的机制。方法将48只SD雄性大鼠随机分成对照组、模型组、尼莫地平组（10.80 mg/kg）、四君子汤组（6 g/kg），每组12只。运用大脑中动脉栓塞法制备大鼠FCIR模型，对照组和模型组给予生理盐水，其它各组则用相应药物连续灌胃14 d。运用Zea-Longa 5级评分法评定FCIR大鼠神经功能，免疫组化检测层粘连蛋白（laminin,LN）、组织金属蛋白酶抑制剂1（tissue inhibitor of matrix metalloproteinases 1,TIMP1）和基质金属蛋白酶9（matrix metalloproteinases 9, MMP9）表达。结果与对照组比较，模型组神经功能评分显著增加（P<0.01）；与模型组比较，四君子汤组、尼莫地平组神经功能评分均明显减少（P<0.01），且四君子汤组、尼莫地平组组间差异无统计学意义（P>0.05）。模型组大脑皮质LN阳性表达明显低于对照组（P<0.01），四君子汤和尼莫地平组LN阳性表达明显高于模型组（P<0.01）。模型组大脑皮质TIMP1、MMP9阳性表达明显高于对照组（P<0.01）。四君子汤和尼莫地平组TIMP1阳性表达明显高于模型组（P<0.01），而MMP9阳性表达明显低于模型组（P<0.01）。结论四君子汤可能通过促进LN和 TIMP1表达，抑制MMP9表达，减轻大鼠的神经功能症状，进而对FCIR大鼠大脑皮质起到神经保护作用。

Neuroprotective Effect of Sijunzi Decoction on Cerebral Cortex in FCIR Rats

Objective To explore the mechanism of neuroprotective effect of Sijunzi Decoction on cerebral cortex in focal cerebral ischemia-reperfusion (FCIR) rats. Methods 48 male Sprague Dawley (SD) rats were randomly divided into control group, model group, nimodipine group and Sijunzi Decoction group, with 12 rats in each group. The FCIR rat models were established by middle cerebral artery occlusion. The control and model groups were treated with normal saline for 14 d, while nimodipine and Sijunzi Decoction groups were treated with nimodipine (10.80 mg/kg) and Sijunzi Decoction (6 g/kg) for 14 d, respectively. The neural function of FCIR rats was assessed according to five grade scale proposed by Zea-Longa. The expressions of LN, TIMP1 and MMP9 protein were determined by immunohistochemistry. Results Compared with the control group, scores of neural function increased remarkably in model group (P<0.01). Compared with the model group, the scores of nimodipine and Sijunzi decoction groups decreased remarkably (P <0.01), but there was no difference between nimodipine and Sijunzi decoction groups (P>0.05). The expression of LN in model group was lower than that in the control group (P<0.01), while the LN expression in nimodipine and Sijunzi decoction groups was higher than that in the model group (P<0.01). The expression of TIMP1 and MMP9 in the model group was obviously higher than that in the control group (P<0.01). The TIMP1 postive expression of nimodipine and Sijunzi decoction groups was obviously higher than that in model group (P<0.01), while the expressiom of MMP9 was lower than that in the model group (P<0.01). Conclusion The neuroprotective effect of Sijunzi Decoctioon on cortex in FCIR rats may be by promoting the expression of LN and TIMP1, inhibiting the expression of MMP9, improving the neural function.