摘要：
目的 探讨单唾液酸四己糖神经节苷脂(monosialotetrahexosylganglioside,GMl)对新生大鼠高胆红素血症脑损伤的作用及可能机制.方法 选择7日龄SD新生大鼠120只,随机分为对照组、模型组和干预组各40只,各组根据造模后处死时间不同随机分为6、12、24、48 h和72h5个亚组,每个亚组8只.模型组和干预组通过腹腔注射胆红素溶液100μg/g造模,造模后干预组即刻腹腔注射GMI 10 mg/kg,每天1次共3d.应用原位缺口末端标记法、免疫组织化学法测定不同时间点海马区脑组织细胞凋亡和Bax表达的情况.结果 造模后6h模型组和干预组大鼠海马区脑组织均出现凋亡细胞和Bax表达,其中细胞凋亡指数中位数分别为33.5％和15.4％,Bax阳性细胞平均灰度值分别为157.4±2.8和162.9±2.3;随时间延长凋亡细胞和Bax表达逐渐增多,均于72 h达高峰,其中细胞凋亡指数中位数分别达55.5％和35.5％,阳性细胞平均灰度值分别达127.8±3.6和141.5±2.7;对照组各时间点未见明显凋亡细胞和Bax表达.与模型组比较,干预组各时间点凋亡细胞和Bax表达均明显减少,但Bax表达和细胞凋亡指数仍高于对照组,差异均有统计学意义(P ＜0.001).结论 脑细胞凋亡参与了高胆红素血症脑损伤的进程,其机制与促凋亡蛋白Bax有关;GM1对高胆红素血症脑损伤有保护作用,其机制可能为通过抑制促凋亡蛋白Bax表达,进而减少脑细胞凋亡,最终减轻脑损伤.%Objective To study the influence of GM1 on hyperbilirubinemia-induced brain injury in neonatal rats and its possible mechanism.Method A total of 120 7-day-old Sprague-Dawley (SD) rats were randomly assigned into normal control group (n =40),hyperbilirubinemia group (n =40) and GM1 group (n =40).According to the different duration of hyperbilirubinemia,each group was further assigned into 5 subgroups,6 h,12 h,24 h,48 h and 72 h group (n =8).The model of neonatal rat with hyperbilirubinemia was established injecting bilirubin solution (100 μg/g) intraperitoneally.GM1 (10 mg/kg) was injected intraperitoneally immediately after the model was established in GM1 group.Immunohistochemical method was used to determine the expression of Bax in hippocampus.TUNEL method was used to measure the neural cell apoptosis index (AI) in the brain.Result Six hours after the hyperbilirubinemia model was set up,the expression of Bax and AI in hyperbilirubinemia group and GM1 group were examined.The median of AI were 33.5％ and 15.4％ respectively and the average grey value of Bax positive cells were 157.4 ± 2.8 and 162.9 ± 2.3.Both apoptosis cells and the expression of Bax were gradually increasing,and peaked at 72 h after the model was established.The median of AI were 55.5％ and 35.5％ respectively,and the average grey value of Bax positive cells were 127.8 ± 3.6 and 141.5 ±2.7 in hyperbilirubinemia group and GM1 group.And the expressions of Bax and AI in the control group were nearly undetectable.The expression of Bax and AI in GM1 group were lower than hyperbilirubinemia group,but higher than the control group,the differences were statistically significant (P ＜ 0.001).Conclusion Brain cells apoptosis is influenced by hyperbilirubinemia-induced brain injury and Bax may be involved in the process.GM1 may reduce the brain damage by inhibiting the expression of Bax to reduce the apoptosis of the brain cells.
