【摘要】 目的探讨脂肪间充质干细胞分泌组(ASC-ST)对大鼠颅脑创伤(TBI)后继发脑水肿的影响及其潜在机制。方法将70只SD大鼠随机分为Sham组(n=18)、TBI组(n=26)和TBI+ST组(n=26)。应用电子颅脑损伤仪(e CCI)建立TBI大鼠模型,Sham组只开骨窗;TBI组经尾静脉注射0.3 m L生理盐水,TBI+ST组经尾静脉注射0.2 m LASC-ST和0.1 m L生理盐水,连续注射7 d。在TBI后3、7、14和21 d对TBI和TBI+ST组8只大鼠行神经功能评分(m NSS);每组选取6只大鼠在TBI后3、7和14 d行头颅核磁(MRI)测量表观弥散系数(ADC);采用干湿比重法测量脑水含量并提取损伤周围脑组织总RNA,采用实时定量多聚酶链反应(q RT-PCR)检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6的m RNA表达水平。结果 TBI后14、21 d时,TBI+ST组m NSS评分均低于TBI组(P<0.05)。TBI后3 d,TBI组和TBI+ST组损伤周围皮层(IC)和损伤对侧皮层(CC)的ADC值均高于Sham组(P<0.05);TBI后7d,TBI+ST组IC和损伤侧海马(IH)的ADC值均低于TBI组(P<0.05);TBI后14 d,TBI+ST组IC和CC的ADC值均低于TBI组(P<0.05)。TBI后3 d和7 d,TBI+ST组大鼠脑组织水含量与TBI组差异无统计学意义(P>0.05);TBI后14 d,TBI+ST组大鼠脑组织水含量低于TBI组(P<0.05)。TBI后3 d,Sham组大鼠损伤周围脑组织中IL-6表达显著低于TBI组和TBI+ST组,TBI+ST组TNF-α表达显著低于Sham组和TBI组,TBI组高于Sham组;TBI+ST组与TBI组IL-1β表达均低于Sham组(均P<0.05)。TBI后7 d,TBI+ST组与Sham组IL-6表达均低于TBI组,TBI+ST组低于Sham组;TBI组TNF-α表达高于Sham组;TBI组IL-1β表达高于其余两组,Sham组高于TBI+ST组(均P<0.05)。TBI后14 d,TBI+ST组与Sham组IL-6表达均低于TBI组;TBI+ST组TNF-α表达仍低于其他组;TBI组IL-1β表达仍高于其余两组(均P<0.05)。结论 ASC-ST可通过减少TBI后炎症反应和炎性因子表达,显著改善大鼠TBI后脑水肿状况和神经功能预后,是一种具有较高临床推广价值的生物治疗药物。更多还原

【Abstract】 Objective To investigate the effect of adipose-derived mesenchymal stem cells(ASC-ST) on thesecondary brain edema of rats after traumatic brain injury(TBI) and its potential mechanisms. Methods Seventy SD ratswere randomly divided into three groups: Sham group(n=18), TBI group(n=26) and TBI + ST group(n=26). TBI models wereestablished by electric cortical contusion impactor(e CCI). Rats from sham group only received the craniectomy withoutimpact. Rats from TBI + ST group were injected with 0.2 m L ASC-ST and 0.1 m L normal saline, while rats from TBI groupwere injected with 0.3 m L normal saline through tail veins after TBI. The injection was persisted for 7 days. Modified neurological function scores(m NSS) were performed on 8 rats from TBI and TBI+ST groups at 3, 7 and 14 days after TBI. Sixrats of each groups accepted magnetic resonance imaging(MRI) at 3, 7 and 14 days after TBI. The water content of brain wasmeasured, and total RNA was exacted from brain tissue of the injured lesions. The m RNA expression levels of TNF-α, IL-1β and IL-6 were detected by quantitative real-time polymerase chain reaction(q RT-PCR). Results At 14 and 21 daysafter TBI, rats from TBI + ST group got lower m NSS scores than those from TBI group(P<0.05). At 3 days after TBI,compared with those in Sham group, the ADC values of ipsilateral cortex(IC) and contralateral cortex(CC) were higher inboth TBI and TBI+ST groups(P<0.05). At 7 days after TBI, the ADC values of IC and ipsilateral hippocampus(IH) werelower in TBI + ST group than those in TBI group(P<0.05). At 14 days after TBI, ADC values of IC and CC were lower inTBI + ST group than those in TBI group(P<0.05). At 3 and 7 days after TBI, the water content of brain tissue of TBI groupwas similar with TBI+ST group(P>0.05). At 14 days after TBI, the water content of brain tissue was lower in TBI+ST groupthan that of TBI group(P<0.05). At 3 days after TBI, the expression of IL-6 was extremely lower in Sham group than that inTBI and TBI+ST groups, while expression of TNF-α was higher in TBI+ST group than that in TBI and Sham groups, andexpression of TNF-α was higher in TBI group than that of Sham group(P<0.05). At 7 days after TBI, expressed levels of IL-6 were lower in TBI+ST and Sham groups than those of TBI group, and the expression was lower in TBI+ST group than that inSham group; The more m RNA expression of TNF-α was found in TBI group than Sham group, and more IL-1β than othergroups; The more IL-1β expression was found in Sham group than TBI+ST group(all P<0.05). At 14 days after TBI, bothTBI+ST and Sham groups were found less m RNA of IL-6 than TBI group, TBI+ST group was found less TNF-α expressionthan other two groups, but the expression of IL-1β in TBI group was still higher than that in other groups(all P<0.05).Conclusion ASC-ST can significantly reduce the brain edema of rats after TBI and improve the prognosis of neurologicalfunction by mitigating the inflammatory responses. It is a promising kind of biotherapeutic drug with high clinical value.更多还原