实验性变态反应性神经炎中整合素α6β4的表达及意义

Expression and significance of integrin a6β4 in experimental allergic neuritis

目的 研究实验性变态反应性神经炎(EAN)中整合素α6β4的mRNA表达变化,探讨α6β4与许旺细胞功能状态的关系,以及其表达变化与髓鞘损伤和修复过程的关系。方法 建立Lewis大鼠EAN动物模型,取18只模型鼠坐骨神经,用原位杂交和半定量逆转录-聚合酶链反应(RT-PCR)方法检测模型的不同时期Lewis大鼠神经局部的整合素。α6β4表达,以正常鼠(3只)为空白对照。结果原位杂交结果表明在EAN的发病过程中,α6的表达未见明显变化,而β4的表达在急性期明显减弱,恢复期或后期逐渐恢复。β4表达减弱主要体现为阳性信号的稀疏而不反映为单个信号的量的变化。以GAPDH为内参照,对整合素。α6β4的mRNA水平做半定量分析,结果显示:EAN病变过程中,α6的mRNA表达变化不明显,而β4的mRNA呈现早期减少后期逐渐恢复进而高于正常的变化过程。结论 炎症因素造成了许旺细胞变性损伤,影响其整合素的表达,许旺细胞出现了与胚胎发育过程类似的表型转换。从这个意义上,可以把α6β4看作许旺细胞分化状态的一个标志,至少可以看作是标志EAN病变过程的一个重要分子。α6β4表达变化与髓鞘的损伤和修复过程密切相关。

Objective To investigate the expression of the integrin α6β4 in experimental allergic neuritis (EAN) and the realationship of the integrin α6β4 with functional states of Schwann cells (Sc) as well as the injury and repair of the myelin during EAN. Methods EAN was induced in Lewis rats and sciatic nerves were resected in 18 EAN and 3 normal rats. The expression of tissue integrin α6β4 was analyzed during the course of EAN induction and in controls by in situ hybridizaton and semi-quantitative RT-PCR. Results The detection of integrin α6 and β4 subunit by hybridizaton in situ demonstrated that expression of α6 subunit present no significant changes during the course of EAN, while expression of β4 declined in the early phase, showing less positive signals than those of the control, and restored its expression in the later or recovery phase. The changes of expression of integrin α6 and β4 in EAN were confirmed by semi-quanititative PT-PCR, using GAPDH as the internal standard. Conclusions The degeneration and injury of Sc caused by inflammation affect the expression of integrin, which shows similar changes in Sc during embryogenesis, indicating α6β4 may be a marker of Sc differatiation and at least an important molecule to mark the course of EAN. The expression of α6β4 correlate with the injury and repair of myelin during EAN.