健脑安对血管性痴呆大鼠海马区IL-1β诱导的c-fos蛋白表达的影响

The influence of CGE on expression of IL-1β and c-fos protein in the hippocampus region in rats following cerebral ischemia-reperfusion

目的 :观察健脑安 (CGE)对脑缺血 再灌注大鼠高表达的IL 1β ,c fos蛋白的抑制作用。 方法 :采用左侧大脑中动脉插入丝线结扎方法制造大鼠血管性痴呆模型 ,分成健脑安大 (19.34× 10 3 g·L-1生药 )、中 (9.6 7× 10 3 g·L-1生药 )、小 (4.83× 10 3 g·L-1生药 )剂量组、IL 1ra对照组、假手术组和模型组。中药用 0 .5 %羧甲基纤维素 (CMC)配成水溶液 ,每 10 0g大鼠灌胃给中药溶液 0 .7mL。IL 1ra对照组大鼠在缺血前 30min和缺血后 10min左侧脑室内分别注射rhIL 1ra 10 μg,假手术组注射同等剂量生理盐水 10 μL。假手术组、模型组分别于造模 7d前开始给予中药灌胃 ,分别按照缺血再灌后不同时间点 (0 .5 ,1,2 ,3,4 ,6 ,8,12 ,2 4 ,4 8,72 ,96 ,14 4 ,16 8h)取材。应用免疫组化方法标记实验各组大鼠应用健脑安和IL 1ra后脑组织中海马区IL 1β蛋白和c fos阳性神经元的数量 ,进行组间均数比较。 结果 :与模型组相比 ,健脑安 3个剂量组在不同再灌时间 (2 ,3,4 ,12 ,72h)均具有显著性的抑制IL 1β ,c fos蛋白表达的作用 ,但小、中剂量组的抑制水平不及IL 1ra(P <0 .0 5和P <0 .0 1)。健脑安抑制海马IL 1β蛋白表达 ,2h起效 ,大剂量 (5 31± 15 1.1)和中剂量 (5 89.3± 78.6 )都强于模型组 (6 87.

Objective: To observe inhabiting effect of CGE (compound ginseng extract) on increased expression of IL-1β and c-fos protein following cerebral ischemia-reperfusion. Method:The vascular dementia model was made by middle cerebral artery occlusion for 2 hours. Expression of IL-1β and c-fos were determined by immunohistochemistry in the hippocampus regions in brain tissue at the 0.5 h～7 d after reperfusion. CGE was diluted by CMC and poured into the stomach by 0.7 mL·(100 g) -1 with a high dosage (19.34×10 3 g·L -1 row herbs),a middle dosage (9.67×10 3 g·L -1 ),a low dosage (4.83×10 3 g·L -1 ). There were an IL-1ra (rhIL-1ra 20 μg injected into the left cerebral ventricle),a sham operation (NaCl 20 μL injected into the left cerebral ventricle) and a model as control. Result: Compared with control group,three dose groups (low,middle and high) in CGE showed significant inhibiting effects on the expression of c-fos protein at 2,3,4,12 hours and 3 day following cerebral ischaemic-reperfusion. The level of the inhibiting effects in small and middle groups were lower at all time points than that in IL-1ra group(P<0.05 to P<0.01). CGE inhibited the expression of hippocampus IL-1β protein,taking effect from the 2 h after reperfusion. Both HD group(531±151.1) and MD group(589.3±78.6) showed more obvious effect which lasted until the 72 h compared with the model group(687.6±116.7)(P<0.01 and 0.05). Large dose group(81.3±16.1) showed the same level of the in-hibiting effect on expression of c-fos protein as IL-1ra group (67.2±25.7)from 4 hour on following cerebral ischaemic reperfusion (P>0.05). Conclusion: CGE with function of Yiqi Bushen,Huoxue Huatan has effect of inhibiting up-regulated expression of IL-1β and c-fos protein following cerebral ischemia-reperfusion. However,this effect of CGE starts relatively later than that of IL-1ra . The effect of CGE is associated with its dosage,i e a larger dosage has a better effect on expression of c-fos protein in post-stroke dementia.