CCB对大鼠坐骨神经嵌压性损伤的保护作用及其机制初探

目的：探讨：①急性周围神经嵌压性损伤早期c-fos基因的表达及其对神经病理及神经传导功能的影响;②Ca2＋通道阻滞剂（CCB,氟桂利嗪）对此的干预效应及机制.方法：制作坐骨神经嵌压性损害的大鼠动物模型,予模型大鼠腹腔分别注射氟桂利嗪1mg/Kg、2mg/Kg,或生理盐水5ml/Kg.在嵌压后0、5min、15min、30min、1h、2h和4周时取大鼠坐骨神经、背根神经节（DRG）,采用RT-PCR、病理学、电生理学等方法测定各时点DRG c-fos mRNA水平和第4周时大鼠背根神经节病理变化、坐骨神经传导速度（NCV）和足趾间距,并与对照组比较.结果：①生理盐水组、氟桂利嗪低剂量（FⅠ）和氟桂利嗪高剂量（FⅡ）组坐骨神经c-fos mRNA表达于损伤30min时开始增加、1h达高峰后开始下降、2h时仍高于对照组（P〈0.01）;其中生理盐水组〉FⅠ组〉FⅡ组（P〈0.05/P〈0.01）.②损伤4周时,光镜下DRG病理变化严重程度顺序为：生理盐水组〉FⅠ组〉FⅡ组,对照组未见异常.③损伤4周时坐骨神经NCV,生理盐水组和FⅠ组显著慢于FⅡ组和对照组（P〈0.01）,FⅡ组与对照组间差异无统计学意义（P〉0.05）.④损伤4周时大鼠足趾间距,生理盐水组均明显小于其他3个组（P〈0.01）;FⅡ组、FⅠ组与对照组间相互差异均无统计学意义（P〉0.05）.结论：周围神经嵌压性损害后发生神经病损和神经功能障碍,这可能与c-fos基因表达上调有关;早期应用CCB（氟桂利嗪）可减轻神经损伤、促进神经功能恢复,这可能与CCB阻断了Ca2＋内流过程使早期神经细胞c-fos基因的表达下调有关

The Protective effect and mechanism on Neural lesions by CCB Following Crush Injuries of Sciatic Nerves in Rats

Objective： To study the nervous pathologic changes and neural functions influenced by c-fos expression, the protective effect and mechanism of calcium channel blocker（CCB）flunarizine following sciatic nerve crush injuries in rats. Methods： Sciatic nerves were crushed with pincers to establish the models of sciatic nerve crush injuries in rats. The mRNA of c-fos in dorsal root gang ionic neurons were detected at 0,5 min, 15min, 30min, 1 h, 2h by RT- PCR, and pathology, nerve conduction velocities （NCVs） and toe spaces were examined at week 4 after crush respectively. The relationship of these results was analysed and comparison was used by flunarizine high/low（F I/F Ⅱ ）dose groups with saline group and control group at random. There were 56 rats in each group. SPSS 13.0 was used statistically. Results：①The mRNA of c-los in DRGs of F f ,FⅡand saline groups began to increase at 30 rain,and obtained to peak at l h, then began to fall,but their values were still significantly higher than that in control group at 2h （P〈0.05/P〈0.01）after crush respectively. And the order of values of the mRNA of c-los in these three groups was saline group 〉 F I group 〉 FⅡ group（P〈0.05/P〈0.01）. ①The order of pathological severity of DRGs in each group was saline group 〉 F I group 〉 FⅡ group, and there was no pathological change of DRGs in control group at week 4 after crush. ② At week 4 after crush, the NCVs of saline and F I groups were slower than those of F Ⅱ and control groups（P〈0.01）, while there was no difference between control group and F Ⅱ group（P〉0.05）. ③At week 4 after crush,the toe spaces of saline group were smaller than that of other groups（P〈0.01）, while there was no difference between F I group and F Ⅱgroup（P〉0.05）. Conclusions：The crush injuries of peripheral nerves can induce nervous pathological changes and neural dysfunctions,wich may be relate to overexpression of c-fos in early stage after crush. And the application of CCB in early stage can reduce damages of nerves and improve neural functions, wich may be due to decrease of the expression of c- fos in early stage by reducing of Ca^2＋ influx following application of CCB.