TPO对新生大鼠缺氧缺血性脑损伤的保护作用

Protection of TPO in neonatal rats with hypoxic ischemic brain damage

目的:观察外源性促血小板生成素(TPO)对新生大鼠缺氧缺血性脑损伤后脑功能的保护作用.方法:7日龄SD大鼠随机分成对照组(C组)、TPO治疗组、缺氧缺血(HIBD)组.于10、14、21日龄检测脑质量损伤百分比、皮层脑组织HE染色、免疫组化观察皮层神经元巢蛋白(Nestin)的表达;14、21、28、35日龄检测脑干诱发电位(BAEP).结果:与对照组相比较,HIBD组大鼠可见损伤侧的脑皮质组织学分层消失、结构紊乱,切片中出现大量条索状空洞,高倍镜下核异常深染、核固缩;TPO治疗组能明显改善大鼠脑组织形态变化;TPO治疗组在各取样时间点的脑质量损伤百分比均分别小于HIBD组(P<0.05).HIBD组大鼠造模3 d后可见少量Nestin蛋白阳性表达出现在神经细胞胞浆、轴突和树突内,造模后第7天Nestin的阳性表达达到高峰;在相同时间点TPO治疗组Nestin的阳性表达与HIBD组趋势相似.BAEP检测发现,TPO治疗组各日龄绝大部分的波峰潜伏期(PL)与对照组相比无明显差异(除21日龄的Ⅲ波,28日龄的Ⅱ-Ⅲ波,35日龄的Ⅱ-Ⅳ波外);从14日龄起TPO治疗组绝大部分的PL与HIBD组相比显著缩短(P<0.05,除14日龄的Ⅴ波尚未能测出外);14日龄起,HIBD组大鼠各波峰间潜伏期(IPL)均明显长于对照组(P<0.05),TPO治疗组大鼠的大部分IPL相比HIBD组明显缩短(P<0.05,14日龄的各个IPL,28日龄的Ⅲ-Ⅴ除外).结论:外源性TPO能够在HIBD发生早期起到神经保护的作用,减轻缺氧缺血导致的脑功能损伤.

Aim: To observe the brain function improvement of application of exogenous thrombopoietin( TPO) in hypoxic ischemic brain damage( HIBD) rats. Methods: Sprague-Dawley rats( 7-day old) were randomly divided into sham operation group( C group),TPO treatment group and HIBD group. The percentage of brain quality damage,pathological changes and the expression of the nestin were detected after birth 10 d,14 d and 21 d by morphological method and immunohistochemistry method. Brainstem auditory evoked potential( BAEP) were recorded after birth 14 d,21 d,28 d and 35 d. Results: Compared to sham operation group,the mice in HIBD group showed apparent histopathological changes in-cluded neuron necrosis,vacuolization and karyopyknosis etc.,but these were much slighter in TPO treatment group. The loss of the percentage of brain quality damage improved significantly in TPO treatment group compared HIBD group( P < 0. 05) at every sampling point. The number of nestin positive cells in TPO and HIBD group were more than C group at every sampling point( P < 0. 05). There were no significant difference of peak latency( PL) of BAEP in TPO treatment group and sham control group expect Ⅲ wave in 21 days,Ⅱ-Ⅲ wave in 28 days and Ⅲ-Ⅳwave in 35 days. There were significant longer( P < 0. 05) of PL in HIBD group compared TPO treatment group after 14 days( expect Ⅴ wave in 14days). There were significant longer of interpeak latency( IPL) in HIBD group compared with sham operation group( P < 0. 05) and TPO treatment group( P < 0. 05). Conclusion: In the early stage of HIBD,the administered immediately with thrombopoietin can play a neuroprotective role,reducing neuronal necrosis and improved the brain dysfunction.