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目的:探讨亮氨酸丰富重复激酶2(LRRK2)对大鼠脑出血神经行为与神经元的影响。方法:SD大鼠30只随机分为假手术组、模型组、干预组,每组10只,通过向脑内注入自体动脉血制备脑出血大鼠模型,模型组按照上述方法造模,假手术组脑内注射无菌生理盐水,干预组在造模6 h前腹腔注射LRRK2抑制剂GNE-7915。造模后第3 d,采用神经行为学评分评价各组神经行为学能力,采用蛋白质印迹法检测各组脑组织中LRRK2蛋白表达量,采用尼氏染色检测各组神经元细胞大小,采用原位末端标记法(TUNEL)检测各组TUNEL阳性细胞数。结果:模型组LRRK2蛋白表达量、神经行为学评分、TUNEL阳性细胞数[(2.62±0.86)、(4.49±1.23)分、(6.22±2.48)个/视野]高于假手术组[(0.45±0.09)、(0.60±0.07)分、(0.92±0.06)个/视野](n P<0.05),干预组LRRK2蛋白表达量、神经行为学评分、TUNEL阳性细胞数[(1.53±0.45)、(2.25±0.69)分、(3.59±1.45)个/视野]低于模型组[(2.62±0.86)、(4.49±1.23)分、(6.22±2.48)个/视野](n P<0.05);模型组神经元细胞大小[(200.41±23.30)μmn 2]低于假手术组[(302.48±48.87)μmn 2](n P<0.05),干预组神经元细胞大小[(248.36±32.26)μmn 2]高于模型组[(200.41±23.30)μmn 2](n P<0.05)。n 结论:抑制LRRK2能够减少脑出血大鼠神经元凋亡,改善神经行为学能力。“,”Objective:To investigate the effect of leucine-rich repeat kinase 2 (LRRK2) on neurobehaviors and neurons in rats with cerebral hemorrhage.Methods:Thirty SD rats were randomly divided into sham operation group, model group, and intervention group (n n=10 each) . Rat models of cerebral hemorrhage were prepared by intracerebral injection of autologous arterial blood, as performed in the model group. The sham operation group received intracerebral injection of sterile normal saline. The intervention group was intraperitoneally injected with LRRK2 inhibitor GNE-7915 at six hours prior to modeling. On day 3 after modeling, the three groups were evaluated for neurobehavioral performance by using neurobehavioral score, measured for the protein expression level of LRRK2 by Western blotting, and observed for the size of neurons by Nissl staining. In-situ TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to examine the number of TUNEL-positive cells in each group.n Results:The LRRK2 protein expression level, neurobehavioral score (points) , TUNEL positive cells in the model group were[ (2.62±0.86) , (4.49±1.23) , (6.22±2.48) /field], respectively, which were higher or more than those in the sham operation group[ (0.45±0.09) , (0.60±0.07) , (0.92±0.06) /field] (n P<0.05) . The intervention group showed lower LRRK2 protein expression and neurobehavioral score, fewer TUNEL positive cells[ (1.53±0.45) , (2.25± 0.69) , (3.59±1.45) /field] compared with the model group [ (2.62±0.86) , (4.49±1.23) , (6.22±2.48) /field] (n P<0.05) . The model group had smaller neurons size [ (200.41±23.30) μmn 2] compared with the sham operation group [ (302.48±48.87) μm n 2] (n P<0.05) , whereas the intervention group had larger neuron size [ (248.36±32.26) μmn 2] compared with the model group [ (200.41) ±23.30) μm n 2] (n P<0.05) .n Conclusion:Inhibiting LRRK2 may lead to ameliorated neuron apoptosis, and thereby improve neurobehavioral capacity in rats with cerebral hemorrhage.