Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage
Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage
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DOI：
10.1111/j.1471-4159.2006.03697.x
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Roh, JK
中科院分区：
文献类型：
--
作者：
Lee, ST;Chu, K;Roh, JK
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、毒性和炎症性损伤中具有组织保护作用。本研究探讨了促红细胞生成素（EPO）对实验性脑出血（ICH）的影响。在通过立体定位输注胶原酶诱导ICH后2小时，腹腔内给予重组人EPO（500或5000 IU/kg，ICH + EPO组）或PBS（ICH +赋形剂组），然后每天一次，持续1或3天。ICH + EPO组在转棒和改良肢体放置试验中均显示出更好的功能恢复。与ICH +溶媒组相比，ICH + EPO组脑含水量呈剂量依赖性降低。EPO对脑含水量的影响可被L-硝基精氨酸甲酯盐酸盐（L-NAME，10 mg/kg）所抑制。ICH + EPO组的平均出血量也减少。EPO可减少血肿周围区TUNEL +、髓过氧化物酶+或OX-42 +细胞的数量。此外，EPO降低TNF-α，Fas和Fas-L的mRNA水平，以及caspase-8，9和3的活性。EPO处理后，内皮型一氧化氮合酶（eNOS）、p-eNOS、pAkt、pSTAT 3和pERK水平上调。这些数据表明，EPO治疗ICH诱导更好的功能恢复，减少血肿周围炎症和细胞凋亡，加上eNOS，STAT 3和ERK的激活。
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.