局部应用PLGA-缓释地塞米松对高温高湿环境下大鼠创伤性脑水肿治疗的研究

Treatment of traumatic cerebral edema in rats with local polylactide acid-glycolic acid copolymer-dexamethasone under high temperature and humidity environment

目的研究高温高湿环境下局部应用聚乳酸羟基乙酸(Polylactide acid-glycolic acid copolymer,PLGA)-缓释地塞米松对实验大鼠颅脑损伤的治疗作用及可能机制。方法成年健康雄性SD大鼠24只,随机分为局部PLGA-缓释地塞米松组,甘露醇组和空白对照组。采用Feeney自由落体法建立大鼠急性颅脑损伤模型后置入高温高湿环境中(35℃、RH 85%)。甘露醇组动物分别于致伤后立即接受2g/kg剂量的静脉注射,并于6h后追加维持剂量1次。24h后以干湿重法测量脑含水量变化,免疫组化和原位杂交方法分析测定AQP4蛋白和mRNA的表达。结果与空白对照组比较,大鼠颅脑损伤后PLGA-地塞米松和甘露醇静脉注射组能显著降低AQP4的表达和脑组织含水量(P<0.05),AQP4-mRNA的表达两组差异无统计学意义(P>0.05)。结论局部应用PLGA-地塞米松可减轻高温高湿环境下创伤性脑水肿的生成,能减少脑水肿周围AQP4及mRNA的表达,影响AQP4表达,从而改变创伤区周围水的转运,使脑创伤后脑组织水肿减轻。

Objective To study the therapeutic effect of local polylactide acid-glycolic acid copolymer （PLGA）-dexamethasone on traumatic cerebral edema（TCE） in rats under high temperature （HT） and high humidity （HH） environment and its possible mechanism. Methods Twenty-four healthy adult SD rats were randomly divided into local PLGA-dexamethasone group, mannitol group, and control group （8 in each group）. An acute cerebral injury model of mice was established by placing them in an HT（35°C ） and HH （RH 85 %） environment with the free-falling body method. Rats in mannitol group were given mannitol（2g/kg） immediately after injury through veins and a maintenance dose was added after 6h. Cerebral water content （CWC） was measured with the dry-wet method after 24h. Expression of AQP4 protein and AQP4 mRNA was detected by immunohistochemistry and in situ hybridization, respectively. Results The expression level of AQP4 and CWC was significantly lower in PLGA- dexamethasone group and mannitol group than in control group （P〈0.05）. However, no significant difference was found in expression of AQP4mRNA between the two groups（P〉0.05）. Conclusion Local PLGA-dexamethasone can decrease the incidence of TCE and the expression of AQP4 and AQP4 mRNA by changing the water transportation around TCE.