Zhang Qin, Hu Wenzhi, Meng Bin, Tang Tiansi
Department of Orthopaedics, First Affiliated Hospital of Soochow University, Soochow 215006, China.
Neurol Res. 2010 Oct;32(8):852-9. doi: 10.1179/016164110X12556180206112. Epub 2010 Mar 26.
Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARγ which is shown to induce neuroprotection in animal models of focal ischemia and traumatic brain injury. SCI is induced by the application of vascular clips (force of 24 g) to the dura via a four-level T(5)-T(8) laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of rosiglitazone, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) apoptosis (terminal deoxynucleotidyl transferase-mediated UTP end labeling staining and electron microscopy); (4) proinflammatory cytokines TNF-α and IL-β; (5) PPARγ, HSP70 and HSP27 expressions. To elucidate whether the protective effects of rosiglitazone were mediated via the estrogen receptors, we investigated the effect of a PPARγ antagonist, GW9662, on the protective effects of rosiglitazone. GW9662 significantly antagonized the effect of the rosiglitazone and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of rosiglitazone after SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.
脊髓损伤（SCI）会导致损伤平面以下功能丧失。原发性损伤后的继发性损伤包括一系列生化和细胞改变，导致组织坏死和细胞死亡。过氧化物酶体增殖物激活受体γ（PPARγ）是核激素受体超家族的一种配体激活转录因子。噻唑烷二酮类药物罗格列酮是PPARγ的强效激动剂，已证明其在局灶性缺血和创伤性脑损伤动物模型中具有神经保护作用。通过四级T（5）-T（8）椎板切除术对硬脑膜施加血管夹（24克力）诱导脊髓损伤。为了更好地了解罗格列酮抗炎作用的作用机制，评估了炎症过程的以下终点：（1）脊髓炎症和组织损伤（组织学评分）；（2）中性粒细胞浸润（髓过氧化物酶活性）；（3）细胞凋亡（末端脱氧核苷酸转移酶介导的UTP末端标记染色和电子显微镜检查）；（4）促炎细胞因子TNF-α和IL-β；（5）PPARγ、HSP70和HSP27表达。为了阐明罗格列酮的保护作用是否通过雌激素受体介导，我们研究了PPARγ拮抗剂GW9662对罗格列酮保护作用的影响。GW9662显著拮抗罗格列酮的作用，并消除了对脊髓损伤的保护作用。综上所述，我们的结果清楚地表明，脊髓损伤后给予罗格列酮可减少与脊髓创伤相关的炎症和组织损伤的发展。
