P2X7受体敲除对小鼠骨癌痛的影响

发布时间：2018-01-06 14:18

本文关键词：P2X7受体敲除对小鼠骨癌痛的影响　出处：《生理学报》2016年03期 　论文类型：期刊论文

【摘要】：癌痛是临床晚期恶性肿瘤患者常见的临床表现之一。其中,以肺癌、乳腺癌和前列腺癌等骨转移引起疼痛尤为严重。P2X7受体是ATP门控离子通道型嘌呤能受体的一个亚型,在脊髓背角主要表达在胶质细胞。P2X7受体激活可以促进胶质细胞释放多种炎症介质,介导脊髓中枢敏化。该受体在炎症痛及神经病理性疼痛中的作用已多有报道,但在癌痛中的作用尚有争议。本研究采用C57BL/6J小鼠股骨骨髓腔内接种Lewis肺癌细胞所诱导的骨癌痛小鼠模型,分析对比了野生型小鼠和P2X7受体基因敲除(P2rx7-/-)小鼠骨癌痛的发生、发展。野生型C57BL/6J小鼠股骨骨髓腔内接种Lewis肺癌细胞后,患侧后肢分别在第7和14天开始出现明显的触诱发痛和热痛过敏,并呈进行性加重;Cat Walk步态分析显示骨癌第21和28天,小鼠患侧脚印面积明显减小,站立时相持续时间缩短,举步时相持续时间显著延长;组织病理学结果显示受累骨骨髓腔有大量肿瘤细胞浸润,骨髓质正常结构消失,伴有髓质骨和皮质骨的破坏。与研究设计时的预期相反,P2rx7-/-小鼠接种瘤细胞后,患肢痛行为检测结果与野生型小鼠相似,甚至在Cat Walk步态分析检测值变化发生的时间上较野生小鼠有所提前。这与本研究组前期在大鼠骨癌痛模型观察到的阻断P2X7受体明显对抗骨癌痛的结果完全不同,提示P2X7受体在大、小鼠骨癌痛中可能发挥不同的作用,并再次提示疾病动物模型上的研究结果与人类疾病机理之间还存在巨大差异。
[Abstract]:Cancer pain is one of the common clinical manifestations in patients with advanced malignant tumor. The pain caused by bone metastases such as breast cancer and prostate cancer is especially severe. P2X7 receptor is a subtype of ATP gated ion channel purinergic receptor. In the dorsal horn of spinal cord, the activation of glial. P2X7 receptor can promote the release of many inflammatory mediators by glial cells. Mediates the central sensitization of the spinal cord. The role of the receptor in inflammatory pain and neuropathic pain has been reported. However, the role of cancer pain is still controversial. In this study, C57BL / 6J mouse femur medullary cavity inoculated with Lewis lung cancer cells induced by bone cancer in mice model. The occurrence of bone cancer pain in wild type mice and P2X7 receptor gene knockout mice was compared. Development. After intramedullary inoculation of Lewis lung cancer cells in the femur of wild-type C57BL / 6J mice, obvious touch-induced pain and hyperalgesia began to appear in the affected hind limbs on the 7th and 14th day, respectively. And progressive aggravation; Cat Walk gait analysis showed that on the 21st and 28th days of bone cancer, the footprint area of the affected side was significantly decreased, the duration of standing phase was shortened, and the duration of walking phase was significantly prolonged. Histopathological results showed that a large number of tumor cells infiltrated the medullary cavity of the involved bone, and the normal structure of the bone marrow disappeared with the destruction of the medullary bone and cortical bone. P2rx7-r- mice inoculated with tumor cells showed similar results to wild-type mice. Even in Cat. The change of gait value of Walk was earlier than that of wild mice. This was not the same as the result of blocking P2X7 receptor in rat bone cancer pain model. Same. These results suggest that P2X7 receptors may play different roles in bone cancer pain in rats and mice, and that there is a great difference between the results of animal models of disease and the mechanism of human diseases.
【作者单位】：复旦大学脑科学研究院;
【基金】：supported by the National Natural Science Foundation of China(No.81471130,31271183,81571064)
【分类号】：R738.1
【正文快照】： 癌痛即恶性肿瘤所引起的疼痛,是慢性痛中最严重也最难以控制的疼痛之一。许多常见的肿瘤如乳腺癌、肺癌、前列腺癌等容易发生骨转移,约有75%~95%的转移性骨癌患者伴有严重疼痛[1],极大降低了患者的生活质量,也给临床治疗带来很多困扰。在目前常用的“三阶梯”癌痛管理治疗手段

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