Rosuvastatin, known as a cholesterol-lowering agent, has been used as an alternative therapy after the onset of stroke. In this study, neuroprotection and functional recovery of exosomes in combination with rosuvastatin have been investigated. Sixty adult male Wistar rats were subjected to middle cerebral artery occlusion (MCAO). Exosome at the dose of 100 μg and/or rosuvastatin at the dose of 20 mg/kg/day for 7 days were administered to rats as a therapeutic strategy. The elevated body swing test (EBST) and Garcia score were conducted as behavioral tests for the measurement of functional recovery. The histopathological and immunohistochemical analyses were also performed for the assessment of infarcted volume and neuroprotection in the brain of rats. The real-time PCR method was carried out to determine the relative expressions of the NLRP-3 and NLRP1 genes. After 7 days of treatment with exosome and rosuvastatin in rats which underwent MCAO, the decrease in infarct volume of the animals treated with exosome was more pronounced compared with those treated only with exosome. The combination therapy remarkably lowered the size of infarct volume. Our observation was confirmed by the downregulation of the NLRP1 and NLRP3 genes in response to combinatory treatment of rats induced by MCOA, denoting a lower rate of cell death. The number of GFAP-positive cells were reduced in the exosome-treated group compared with the MCAO group. The rate of lipid peroxidation was measured by malondialdehyde (MDA) levels which demonstrated a significant reduction of MDA in the exosome- and rotuvastatin-treated groups when compared with the MCAO group. However, the levels of the SOD enzyme did not significantly alter when the treatment groups were compared with the MCAO group. According to our findings, it seems that the use of exosomes and rosuvastatin, as a novel treatment regimen, might promote neurological recovery after the onset of stroke.

中文翻译：

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骨髓干细胞外泌体与瑞舒伐他汀联合对缺血性中风大鼠功能恢复和神经保护的影响。

瑞舒伐他汀被称为降胆固醇药，已被用作中风发作后的替代疗法。在这项研究中，已经研究了罗苏伐他汀与外泌体结合的神经保护作用和功能恢复。对60只成年雄性Wistar大鼠进行大脑中动脉闭塞（MCAO）。作为治疗策略，将100μg剂量的外泌体和/或20 mg / kg / day剂量的瑞舒伐他汀治疗7天。进行升高的身体摆动测试（EBST）和加西亚评分作为行为测试，以测量功能恢复。还进行了组织病理学和免疫组织化学分析，以评估大鼠脑梗死体积和神经保护作用。进行了实时PCR方法，以确定NLRP-3和NLRP1基因的相对表达。在接受MCAO的大鼠中用外泌体和瑞舒伐他汀治疗7天后，与仅用外泌体治疗的动物相比，用外泌体治疗的动物梗塞体积的减少更为明显。联合治疗显着降低了梗塞体积的大小。我们的观察结果通过响应MCOA诱导的大鼠联合治疗而降低了NLRP1和NLRP3基因的表达而得到证实，这表明细胞死亡率较低。与MCAO组相比，外来体治疗组的GFAP阳性细胞数量减少。通过丙二醛（MDA）水平来测量脂质过氧化的速率，与MCAO组相比，丙二醛和罗伐他汀治疗组的MDA明显降低。但是，当将治疗组与MCAO组进行比较时，SOD酶的水平没有明显改变。根据我们的发现，似乎将外来体和瑞舒伐他汀作为一种新的治疗方案，可能会促进中风发作后的神经功能恢复。