摘要
目的观察鞘内转染腺相关病毒6-人神经生长因子β(AAV6-hNGFβ)对糖尿病神经病变(DPN)大鼠背神经节损伤修复的影响。方法将72只SD大鼠随机均分为4组,正常组、模型组、hNGFβ组(模型组+AAV6-hNGFβ-EGFP)和阴性对照组(模型组+AAV6-EGFP)。正常组注射等量生理盐水,hNGFβ组、阴性对照组和模型组均建立糖尿病周围神经病变模型,并于造模后分别在鞘内注射AAV6-hNGFβ-EGFP、AAV6-EGFP和等量生理盐水。8周后观察大鼠背根神经节组织形态,并测定不同病程(1周、4周、8周)大鼠坐骨神经传导速度,同时检测背根神经节神经生长因子(NGF)、细胞因子(ICAM-1、TNF-α)的mRNA和蛋白表达水平。结果与正常组比较,模型组大鼠背根神经节尼氏小体明显减少且染色变浅,伴有空泡样变化,神经组织出现损伤,同时坐骨神经传导速度降低,背根神经节NGF表达减少,炎性因子表达增多,差异有统计学意义(P<0.05);模型组和阴性组大鼠以上指标比较均无显著差异;与模型组和阴性对照组比较,hNGFβ组大鼠背根神经节尼氏小体明显增多,坐骨神经传导速度明显提高,背根神经节NGF表达增加,炎性因子表达降低,差异有统计学意义(P<0.05)。结论鞘内转染AAV6-hNGFβ可上调NGF同时抑制细胞因子,从而修复DPN大鼠的神经节损伤。
Objective To observe the effect of intrathecal transfection of AAV6-hNGFβon recovery of dorsal root ganglion in diabetic peripheral neuropathy(DPN)rats.Methods Seventy two male SD rats were randomly divided into four groups:normal group,model group,hNGFβgroup and negative control group.Normal group injection of the same amount of normal saline.DPN model rats were used in hNGFβgroup,negative control group and model group,in which the rats were intrathecal transfected with saline,AAV6-EGFP and AAV6-hNGFβ-EGFP,respectively.The dorsal root ganglion(DRG)tissue in rats was observed after 8 weeks.The sciatic nerve conduction velocity and the expression level of NGF,ICAM-1 and TNF-αof DRG in each group were measured at week 1,4 and 8.Results Compared with normal group,the Nissl corpuscles in model group were reduced and the color was light,accompanied with partial vacuolation,showing that the nerve was damaged.Indeed,in model group,the sciatic nerve conduction velocity was reduced and the expression level of neurotrophic factor NGF was decreased while cytokines ICAM-1 and TNF-αwere both significantly increased in DRG(P<0.05).There was no significant difference in the above indexes between the model group and the negative group.Compared with model group and negative control group,the Nissl corpuscles in hNGFβgroup were increased.In addition,in hNGFβgroup,the sciatic nerve conduction velocity was increased and the expression level of neurotrophic factor NGF was improved while cytokines ICAM-1 and TNF-αwere both significantly decreased in DRG(P<0.05).Conclusion Intrathecal transfection of AAV6-hNGFβ-EGFP could rehabilitate the neurologic damage in DPN rats by increasing the expression of neurotrophic factors and decreasing cytokines in DRG.
作者
罗荔
罗梅
张丽
陆春晖
王敏哲
LUO Li;LUO Mei;ZHANG Li(Department of Endocrinology,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang 830011,China;Department of Cardiology,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang 830011,China)
出处
《临床和实验医学杂志》
2019年第22期2373-2377,共5页
Journal of Clinical and Experimental Medicine
基金
新疆维吾尔自治区自然科学基金项目(编号:2016D01C241)
