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

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.

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

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℃) 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.