首页> 中文期刊>中国药物与临床 >抑制ATP结合盒转运体亚家族C成员8表达促进大鼠脊髓损伤后神经组织修复和神经功能恢复

抑制ATP结合盒转运体亚家族C成员8表达促进大鼠脊髓损伤后神经组织修复和神经功能恢复

     

摘要

Objective To investigate the expression of spinal cord Abcc8 after spinal injury, and the impacts of inhibiting Abcc8 expression restoration of nerve tissue and neural functions in rats with spinal cord injury. Methods Modified Allen weight dropping method was used to cause moderate spinal cord injury in adult female Wistar rats (aged 6 months, 200-220 g). After 5 days, severity of spinal cord injury was examined by HE staining. Immunohistochemical staining was then used to measure the expression of sulfonylurea receptor 1 (SUR1), the product of Abcc8 gene expres-sion in the injured spinal cord tissue. Immediately after spinal cord injury, the rats were given antisense oligonucleotides (ASO) intravenously to inhibit the expression of spinal cord Abcc8. On day 28 after the injury, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate the locomotive functions in rats. HE staining of the spinal cord tissue was performed to measure the area of lesions. Results On day 5 of injury in rats, HE staining showed obvious cavitation and tissue defects of the spinal cord, accompanied by massive inflammatory infiltration and deformation or displacement of residual tissues. Fluorescence immunohistochemical staining showed a significant increase in fluorescence intensity of SUR1 in the penumbral necrotic tissue adjacent to the epicenter of injured spinal cord. On day 28 of spinal cord injury, HE stained area measurement of injured lesions showed that in rats immediately given Abcc8-ASO after spinal cord in-jury, the area of segmental lesion was significantly reduced. BBB rating scale showed significant restoration of hind limb motor function in rats immediately given intravenously Abcc8-ASO after spinal cord injury. Conclusion After spinal cord injury, the expression of spinal cord Abcc8 is elevated in rats. Inhibiting the expression of Abcc8 may significantly promote restoration of nerve tissue and neural functions in rats after spinal cord injury.%目的:探究大鼠脊髓损伤发生后,损伤脊髓组织内ATP结合盒转运体亚家族C成员8(Abcc8)基因表达量变化及抑制Abcc8表达对脊髓损伤大鼠神经组织和神经功能恢复的影响。方法采用改良的Allen重物坠落打击法造成成年雌性Wistar大鼠(6月龄,200~220 g)中度脊髓损伤5 d后,通过苏木精-伊红(HE)染色检测脊髓损伤程度,通过免疫组织化学染色检测损伤脊髓组织内Abcc8基因表达产物磺脲受体1(SUR1)的表达量变化。大鼠脊髓损伤后立即通过经静脉给予反义核苷酸(ASO)抑制损伤脊髓内Abcc8基因表达,大鼠脊髓损伤28 d后通过Basso Beattie Bresnahan(BBB)评分评价大鼠运动功能,通过HE染色检测脊髓组织损伤区域面积。结果大鼠脊髓损伤5 d后,HE染色显示,损伤脊髓组织出现明显空洞和组织缺损,伴有多量炎细胞浸润和残存组织变形移位。免疫组织化学染色(荧光法)显示,大鼠脊髓损伤中心区域邻近坏死组织的半暗区内SUR1抗原荧光强度显著增加。大鼠脊髓损伤28 d后的HE染色-损伤区域面积测定显示,脊髓损伤后立即接受Abcc8-ASO治疗的大鼠脊髓损伤节段病灶面积明显减少。 BBB运动功能评分显示,脊髓损伤发生后即进行Abcc8-ASO静脉注射治疗的大鼠的后肢运动功能恢复显著增强。结论大鼠脊髓损伤后,损伤脊髓组织内Abcc8基因表达量上升,抑制Abcc8表达对脊髓损伤大鼠神经组织和神经功能的恢复具有显著促进作用。

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