骨髓间充质干细胞移植对血管性痴呆大鼠认知功能及一氧化氮合酶的表达的影响

Effect of mesenchymal stem cells transplantation on cognitive function and expression of nitric oxide synthase of vascular dementia rats model

目的探讨骨髓间充质干细胞(BMSCs)侧脑室移植对血管性痴呆(Va D)大鼠认知功能及一氧化氮合酶(NOS)的表达的影响。方法将SD大鼠分为BMSCs组、培养基组及假手术组。BMSCs组大鼠侧脑室注射BMSCs,培养基组大鼠侧脑室注射DMEM基础培养液。移植后30 d比较各组大鼠学习记忆能力,血浆和海马组织TNOS和i NOS的酶活性及NO水平、血液NOS mRNA、海马组织NOS mRNA、NOS蛋白水平。结果与假手术组比较,BMSCs组及培养基组逃避潜伏期及第1次穿越平台时间显著延长(均P<0.05),穿越平台次数明显减少(P<0.05)。与培养基组比较,BMSCs组大鼠逃避潜伏期及第1次穿越平台时间显著缩短(均P<0.05),穿越平台次数显著增加(均P<0.05)。培养基组和BMSCs组大鼠血浆、海马组织t NOS、i NOS酶活性及NO水平均显著高于假手术组(均P<0.05)。BMSCs组大鼠血浆、海马组织t NOS、i NOS酶活性及NO水平均明显低于培养基组(均P<0.05)。与假手术组比较,培养基组和BMSCs组血浆、海马组织NOS mRNA及海马组织NOS蛋白表达水平均显著增高(均P<0.01)。BMSCs组血浆、海马组织NOS mRNA及海马组织蛋白NOS表达水平较培养基组显著降低(均P<0.05)。结论 BMSCs侧脑室移植能够降低Va D大鼠的NO水平及t NOS、i NOS酶活性,从而发挥一定神经保护作用,改善大鼠的认知功能。

Objective To investigate the effects of bone marrow meseuehymal stromal cells （BMSCs） transplantation on cognitive function and expression of nitric oxide synthase （NOS） of vascular dementia （ VaD ） rat model. Methods The SD rats were divided into BMSCs group, medium injection group and sham operation group. The rat of BMSCs were injected with BMSCs, and the rats of medium injection group were injected with DMEM. At 30 d after transplantation, learning and memory ability, enzyme activity of TNOS, iNOS and the content of NO in plasma and hippoeampus, expression of NOS mRNA in blood, expression of NOS mRNA and protein in hippoeampus were compared between three groups. Results Compared with sham operation group, the escape latent period and the time of first crossing the platform prolonged of BMSCs group and medium injection group were significantly prolonged （ all P 〈 0. 05 ）, the number of crossing the platform of medium injection group were significantly increased （ P 〈 0. 05 ）. Compared with medium injection group, the escape latent period and the time of first crossing the platform of BMSCs group were significantly shorten （ all P 〈 0. 05 ） , and the number of crossing the platform of BMSCs group were significantly increased （P 〈 0. 05 ）. Enzymatic activity of tNOS, iNOS, and the content of NO in plasma and hippocampus of medium injection group and BMSCs group were significantly increased than those in sham operation group （ all P 〈 0. 05 ）. The enzymatic activity of tNOS, iNOS, and the content of NO in plasma and hippocampus of BMSCs group were significant[y decreased than those in medium injection group （ all P 〈 0.05 ）. Compared with sham operation group, the expression of NOS mRNA in plasma and hippocampus, the expression of NOS protein in hippocampus iNOS of medium injection group and BMSCs group were significantly increased （ all P 〈 0. 01 ）. The expression of NOS mRNA in plasma and hippocampus, the expression of NOS protein in hippocampus iNOS of BMSCs group were significantly decreased than those in medium injection group （ all P 〈 0. 05 ）. Conclusions BMSCs transplantation into lateral ventricle of VaD rats can reduce the level of NO, the enzymatic activity of tNOS, iNOS, so as to prevent the nerve from the injury. It can improve the cognitive impairment of the VaD rats.