摘要
研究目的：观察联合应用乌司他丁(UTI)和甘油果糖对大鼠脑出血后水通道4(AQP4)的影响。
实验方法：健康SD大鼠100只,随机均分为对照组(A组)、脑出血组(B组)、乌司他丁组(C组)、乌司他丁联合甘油果糖组(D组)。除A组外,其他各组采用自体动脉血注入尾状核法制成大鼠脑出血模型,出现神经功能缺损症状视为造模成功。B组于尾静脉微量泵输注8mg/kg生理盐水,C组于尾静脉微量泵脉输注乌司他丁5万u/kg,D组于尾静脉分别注入甘油果糖5ml/kg和乌司他丁5万u/kg,各组均10min内输注完毕,分别在6h、1d、3d、5d、7d时间点处死各5只大鼠。免疫组化法观察AQP4的表达,伊文思蓝法测BBB的通透性,干湿重法计算脑含水量。
结果：与A组相比,各组AQP4于6h开始升高,3d达到高峰,7d仍高于正常,D组明显低于B组(P<0.05)；脑出血后BBB通透性均在出血后6h开始高,1-3d最高,之后逐渐降低,C组低于B组,而D组又显著低于C(P<0.05)；B组脑含水量6h即开始增加,3d达到高峰后缓慢下降,但7d仍高于正常(P<0.05)；D组各时间点含水量均低于C组(P<0.05),于6h降低最明显。
结论：脑出血后可能通过上调APQ,表达,增加B B B通透性,参与脑水肿形成,而早期给予甘油果糖脱水治疗联合应用乌司他丁可明显抑制进展。
Objective To investigate the effect of Ulinastatin combined with glycerol fructose on aquaporin-4 expression in rats after intracerebral hemorrhage.
Methods 100 SD rats were randomly divided into control group(A),intracerebral hemorrhage group (B), Ulinastatin group(C),glycerol fructose and Ulinastatin group(D), In addition to A group,other groups were made of a model of cerebral hemorrhage,using autologous arterial blood into the caudate nucleus of the legal system and symptoms of neurological impairment was a successful model.The B models were established by stereotaxic injection of autologous artery blood into the caudate nucleus. C group was injected intravenously Ulinastatin 50000 u/kg, D Group in the tail vein injection of glycerol fructose 5ml/kg and ulinastatin50000 u/ kg, ICH group given 8ml/kg saline at the same time, each group after modeling, respectively,6h, Id,3d,5d and 7d were killed, each time point,5 rats each. Immunohistochemical expression of AQP4 observed, Evans blue method to measure the blood-brain barrier permeability, brain water content of wet and dry weight method that cerebral edema.
Results Compared with A group, AQP4 began to increase at 6h,3d peak,7d still higher than normal, D group was significantly less than the B group (P<0.05); BBB permeability after 6h in cerebral hemorrhage started to be high,1～3d top, then gradually decreased, BBB permeability after intracerebral hemorrhage were higher after 6h,1～3d maximum, then gradually decreased, C group was lower than B group, but the D group was significantly lower than the C group (P<0.05); B Group brain water content began to increase 6 h,3 d after the peak slow down,7 d still higher than normal (P<0.05); D group water content at all time points were lower than the B group and the C group (P<0.05), the most significant reduction in 6h.
Conclusions Expression by upregulating the APQ 4, increased permeability BBB participate in the formation of brain edema in cerebral hemorrhage, and an early treatment for dehydration of glycerol combined fructose Ulinastatin can inhibit this process.
引文
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