曲美他嗪对急性低压缺氧大鼠脑水肿的预防作用

Preventive effect of trimetazidine on brain edema induced by hypobaric hypoxia in rats

目的研究曲美他嗪(TMZ)对低压缺氧致大鼠脑组织水肿的预防作用。方法将72只雌性SD大鼠随机分为常氧对照组、低压缺氧模型组、尼莫地平(NIM)组和TMZ高、中、低剂量组,每组12只。除常氧对照组外,其他组均应用低压氧舱模拟海拔7 000 m高原、持续12 h建立高原缺氧模型。应用苏木精-伊红(hematoxylin-eosin,HE)染色法观察脑组织形态学变化;物理方法检测脑含水量;反转录聚合酶链式反应(RT-PCR)技术检测各组大鼠脑组织水通道蛋白-4(AQP-4)mRNA的表达;Western blot检测各组大鼠脑组织AQP-4蛋白水平。结果与低压缺氧模型组比较,HE染色显示:NIM组和TMZ各剂量组均可减轻大鼠低压缺氧造成的脑组织损伤,TMZ高剂量组最为显著;NIM组和TMZ各剂量组均可降低低压缺氧大鼠脑含水量,差异有统计学意义(P<0.05),TMZ高剂量组降低更为明显(P<0.01);NIM组和TMZ各剂量组均显著降低脑组织中AQP-4 mRNA及蛋白的表达,差异有统计学意义(P<0.01)。结论 TMZ对急性低压缺氧致大鼠脑水肿具有显著的预防作用,可显著减轻低压缺氧状态造成的大鼠脑组织损伤和脑水肿,其机制可能与其降低脑组织中AQP-4的表达水平有关。

Objective To study the preventive effect of trimetazidine（TMZ） on brain edema induced by hypobaric hypoxia in rats.Methods Seventy-two female SD rats were randomly divided into normal control group,hypobaric hypoxia model group,nimodipine（NIM） group and TMZ high,medium and low dose group,twelve rats in each group.In addition to the normal control group,other groups were underwent the hypobaric hypoxia to simulate altitude 7 000 m plateau in hypobaric chamber for 12 hours,by which the high altitude hypoxia models were established.The brain tissue morphological changes were observed by hematoxylin-eosin（HE）staining;the brain water content was detected by physical methods;the mRNA expression of aquaporin-4（AQP-4） in the brain tissue was detected by reverse transcription-polymerase chain reaction;the protein expression of AQP-4 in the brain tissue was detected by Western blot.Results Compared with the hypobaric hypoxia model group,HE staining,in the NIM and TMZ groups,the brain tissue damage caused by hypobaric hypoxia in rats was alleviative,especially in TMZ high dose group.NIM and TMZ can reduce the brain water content in hypobaric hypoxia rats（P〈0.05）,and especially in the TMZ high dose group（P〈0.01）.NIM and TMZ can reduce the mRNA and protein expression of AQP-4 in brain tissue（P〈0.01）.Conclusion TMZ can prevent the brain edema caused by hypobaric hypoxia in rats,and can relieve the brain tissue damage and brain edema,which may be related with down-regulating of the expressions of AQP-4 in brain.