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目的探讨腹腔注射不同剂量三碘甲腺原氨酸(T3)对新生小鼠兴奋毒性脑损伤脑组织病理改变和Caspase-3、髓鞘碱性蛋白(MBP)表达的影响。方法 72只新生5日龄(P5)ICR小鼠随机分为PBS对照组(PBS组)、兴奋毒性脑损伤模型组(IA组)、T3低剂量治疗组(LT组)、T3中剂量治疗组(MT组)和T3高剂量治疗组(HT组)。模型组及T3各剂量治疗组脑内注射鹅膏蕈氨酸建立兴奋毒性脑损伤模型,模型建立后腹腔注射3种不同剂量(2μg.kg-1、5μg.kg-1、10μg.kg-1)T3共5 d干预治疗。于脑内注射后120 h(P10)、30 d(P35)各取6只小鼠处死,HE染色观察其脑组织病理改变。免疫组织化学法检测小鼠脑组织损伤区Caspase-3及MBP的表达。结果 P10时,MT组脑白质及皮质损伤较IA组均明显减轻(Pa<0.01),HT组脑皮质损伤较IA组减轻(P<0.05);IA组Caspase-3表达较PBS组明显增强(P<0.001),MT组和HT组Caspase-3表达与IA组比较明显减低(P<0.01);P10和P35时,IA组MBP表达较PBS组均明显减弱(P<0.001),MT组和HT组MBP表达较IA组均明显增强(P<0.05)。LT组脑组织病理损伤程度及Caspase-3、MBP表达与IA组比较差异均无统计学意义(Pa>0.05)。结论腹腔注射中剂量及高剂量T3可减轻小鼠兴奋毒性脑损伤病理损伤程度,减少细胞凋亡,促进髓鞘的形成;低剂量T3对新生小鼠兴奋毒性脑损伤程度、细胞凋亡及髓鞘形成均无影响。
Objective To investigate the effects of intraperitoneal injection of triiodothyronine (T3) on pathological changes of cerebral tissue and expressions of Caspase-3 and MBP in brain of neonatal mice with excitotoxic brain injury. Methods Seventy-two newborn (P5) ICR mice were randomly divided into PBS control group, IA model group, T3 low dose treatment group (LT group), T3 medium dose treatment group (MT group) and T3 high-dose treatment group (HT group). The model group and each dose of T3 treatment group were injected ibotenic acid to establish excitotoxic brain injury model. The model was established by intraperitoneal injection of three different doses (2μg.kg-1, 5μg.kg-1, 10μg.kg-1 ) T3 total 5 d intervention. Six mice were killed at 120 h (P10) and 30 d (P35) respectively after intracerebral injection. The pathological changes of brain tissue were observed by HE staining. Immunohistochemistry was used to detect the expression of Caspase-3 and MBP in brain tissue of mice. Results Compared with the IA group, the injury of cerebral white matter and cortex in MT group was significantly reduced (P <0.01), and the cortical injury in HT group was less than that in IA group (P <0.05). The expression of Caspase-3 in IA group was significantly increased (P <0.001). The expression of Caspase-3 in MT group and HT group was significantly lower than that in IA group (P <0.01). At P10 and P35, the expression of MBP in IA group was significantly lower than that in PBS group The expression of MBP in HT group was significantly higher than that in IA group (P <0.05). There were no significant differences in the degree of pathological damage and the expressions of Caspase-3, MBP between LT group and IA group (P> 0.05). Conclusion Intraperitoneal injection of medium dose and high dose of T3 can reduce the degree of pathological damage of excitotoxic brain injury in mice, reduce apoptosis and promote the formation of myelin. The effect of low dose T3 on the degree of acute brain injury, apoptosis, Sheath formation had no effect.