粉防己碱对微波辐射致纹状体损伤的治疗作用及机制探讨

Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation

目的研究粉防己碱(TET)对微波辐射致纹状体损伤的治疗作用及其机制。方法以40只C57BL/6N小鼠为实验对象,采用随机数表法将小鼠分为空白对照组(C)、辐射对照组(R)、TET组(TET)和TET+辐射组(TET+R),每组10只。接受辐射小鼠采用2.856 GHz、8 mW/cm2微波全身辐射15 min,建立微波辐射纹状体损伤的动物模型。接受TET给药小鼠给予腹腔注射TET(60 mg/kg),1次/d,连续3 d。采用紫外分光光度法验证TET结构。利用旷场实验,检测小鼠焦虑情绪。通过光镜和透射电镜观察纹状体组织病理学和超微结构变化。采用实时荧光定量聚合酶联反应(qPCR)检测各组小鼠纹状体电压门控钙通道(VGCC)亚型基因表达改变。结果微波辐射后,小鼠探索中央区域时间、路程均较辐射前明显降低(t=4.60、5.18,P<0.01),TET给药后显著改善(F=1.43、4.37,P<0.05)。辐射后7 d,可见纹状体部分神经元核固缩、深染,以苍白球区(GP)较为明显。部分神经元凋亡,胶质细胞线粒体肿胀、空化,突触间隙模糊,血管周隙增宽。TET给药后上述病变均明显改善。微波辐射及TET给药对纹状体VGCC各亚型基因表达均无显著影响(P>0.05)。结论TET对微波辐射致小鼠焦虑样行为及纹状体组织结构损伤均具有一定治疗作用,其作用机制与纹状体VGCC基因表达无关。

Objective To study the therapeutic effect Tetrandrine(TET)on striatal injury caused by microwave radiation and underlying mechanism.Methods C57BL/6N mice were randomly divided into blank control group(C),radiation control group(R),TET group(TET)and TET combined with radiation group(TET+R).The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min.TET(60 mg/kg)was injected intraperitoneally once a day for 3 consecutive days.The TET structure was verified by ultraviolet spectrophotometry.The open field experiment was used to detect the change of anxiety in mice.Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy(TMT).Quantitative real-time PCR(qPCR)was used to detect gene expression changes of voltage-gated calcium channel(VGCC)subtype in the striatum.Results The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation(t=4.60,5.18,P<0.01),and the TET administration significantly improved these changes(F=1.43,4.37,P<0.05).7 d after microwave radiation,some neuronal nuclei in the striatum of mice contracted and could be stained deeply,which was more obvious in the globus pallidus area.The partial neuronal apoptosis,swelling and cavitation of glial cell mitochondria,blurring of synaptic gaps,and widening of perivascular gaps in the striatum were observed by TMT.The above lesions were significantly rescued after TET administration.But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC(P>0.05).Conclusions TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation,which is independent of the expression of striatal VGCC genes.