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目的探讨纳络酮预处理对脑出血大鼠的保护效应及相关作用机制。方法将30只雄性Sprague-Dawley大鼠(体质量280～350g)按随机数字表法随机分为假手术对照组(Sham组)、脑出血(intracere bralhemorrhage,ICH)组和纳络酮预处理(Naloxone preconditioning,NP)组,每组10只大鼠。复制上述动物模型之前,NP组大鼠预先给予盐酸纳络酮(2.0mg/kg),ICH组给予相同体积的生理盐水,随后制备ICH模型。切取并收集大鼠脑出血灶周围脑组织,分别采用RT-PCR和Westernblot检测大鼠病变脑组织中水通道蛋白(aquaporin protein4,AQP4)在转录水平和蛋白水平上的变化情况;同时采用免疫组织化学检测大鼠病变脑组织中基质金属蛋白酶(matrix metalloproteinase9,MMP-9)的阳性表达情况。结果相对于Sham组,ICH组大鼠脑组织中含水量明显增加(P<0.05),而经过纳络酮预处理后,大鼠脑组织中含水量明显减少(P<0.05);相对于ICH组,NP可有效降低脑出血大鼠脑组织中AQP4mRNA和蛋白水平(P<0.01);同时,NP组大鼠脑组织中MMP-9阳性表达率明显下调(P<0.01)。结论纳络酮作为脑出血的一种有效的保护措施,其具体作用机制可能与其降低脑组织中AQP4的表达,从而减少脑水肿的发生及下调的MMP-9水平密切相关。
Objective To investigate the protective effect of naloxone preconditioning on intracerebral hemorrhage in rats and its related mechanisms. Methods Thirty male Sprague-Dawley rats (body weight 280-350g) were randomly divided into Sham group, intracerebral hemorrhage (ICH) group and naloxone pretreatment Naloxone preconditioning, NP) group, 10 rats per group. Before replicating the animal model, NP rats were pretreated with naloxone HCl (2.0 mg / kg), ICH rats were given the same volume of saline, and ICH model was prepared. The brain tissue around the cerebral hemorrhagic foci in rats was cut and collected. The changes of aquaporin protein4 (AQP4) in rat brain tissues were detected by RT-PCR and Western blot respectively. Meanwhile, The positive expression of matrix metalloproteinase 9 (MMP-9) in the diseased brain of rats was detected by chemical method. Results Compared with Sham group, the water content of brain tissue in ICH group was significantly increased (P <0.05), while after naloxone preconditioning, the water content in brain tissue was significantly decreased (P <0.05); Compared with ICH NP could effectively reduce the level of AQP4mRNA and protein in the brain tissue of ICH rats (P <0.01). Meanwhile, the positive rate of MMP-9 in the NP group was significantly decreased (P <0.01). Conclusion Naloxone is an effective protective measure for cerebral hemorrhage. Its specific mechanism may be related to the decrease of AQP4 expression in brain tissue and the decrease of cerebral edema and the down-regulated MMP-9 level.