Lee Soon-Tae, Chu Kon, Sinn Dong-In, Jung Keun-Hwa, Kim Eun-Hee, Kim Se-Jeong, Kim Jeong-Min, Ko Song-Yi, Kim Manho, Roh Jae-Kyu
Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
J Neurochem. 2006 Mar;96(6):1728-39. doi: 10.1111/j.1471-4159.2006.03697.x.
Erythropoietin (EPO), a pleiotropic cytokine involved in erythropoiesis, is tissue-protective in ischemic, traumatic, toxic and inflammatory injuries. In this study, we investigated the effect of EPO in experimental intracerebral hemorrhage (ICH). Two hours after inducing ICH via the stereotaxic infusion of collagenase, recombinant human EPO (500 or 5000 IU/kg, ICH + EPO group) or PBS (ICH + vehicle group) was administered intraperitoneally, then once daily afterwards for 1 or 3 days. ICH + EPO showed the better functional recovery in both rotarod and modified limb placing tests. The brain water content was decreased in ICH + EPO dose-dependently, as compared with ICH + vehicle. The effect of EPO on the brain water content was inhibited by N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg). Mean hemorrhage volume was also decreased in ICH + EPO. EPO reduced the numbers of TUNEL +, myeloperoxidase + or OX-42 + cells in the perihematomal area. In addition, EPO reduced the mRNA level of TNF-alpha, Fas and Fas-L, as well as the activities of caspase-8, 9 and 3. EPO treatment showed up-regulations of endothelial nitric oxide synthase (eNOS) and p-eNOS, pAkt, pSTAT3 and pERK levels. These data suggests that EPO treatment in ICH induces better functional recovery with reducing perihematomal inflammation and apoptosis, coupled with activations of eNOS, STAT3 and ERK.
促红细胞生成素（EPO）是一种参与红细胞生成的多效性细胞因子，在缺血性、创伤性、中毒性和炎性损伤中具有组织保护作用。在本研究中，我们调查了EPO在实验性脑出血（ICH）中的作用。通过立体定向注射胶原酶诱导ICH两小时后，腹腔注射重组人EPO（500或5000 IU/kg，ICH + EPO组）或PBS（ICH + 载体组），之后每天注射一次，持续1或3天。在转棒试验和改良肢体放置试验中，ICH + EPO组均显示出更好的功能恢复。与ICH + 载体组相比，ICH + EPO组脑含水量呈剂量依赖性降低。盐酸N（ω）-硝基-L-精氨酸甲酯（L-NAME，10 mg/kg）可抑制EPO对脑含水量的影响。ICH + EPO组的平均出血量也有所减少。EPO减少了血肿周围区域TUNEL +、髓过氧化物酶 + 或OX-42 + 细胞的数量。此外，EPO降低了TNF-α、Fas和Fas-L的mRNA水平，以及caspase-8、9和3的活性。EPO治疗显示内皮型一氧化氮合酶（eNOS）、p-eNOS、pAkt、pSTAT3和pERK水平上调。这些数据表明，ICH中EPO治疗可通过减少血肿周围炎症和细胞凋亡，以及激活eNOS、STAT3和ERK诱导更好的功能恢复。
