高表达瞬时电位受体通道1在大鼠弥漫性轴索损伤中的作用机制.

Objective To investigate the possible role of canonical transient receptor potential channel 1 (TRPC1) after diffuse axonal injury (DAI) and discuss the mechanism of TRPC1 involved in calcium overload of neurons and myelin degeneration after DAI. Methods Rat models of DAI were established with the method of rotational acceleration of the brain. DAI intervention group was established by using SKF96365 intracerebroventricular injection. Intracellular calcium concentration was detected by Fura-2AM. The dynamic expressions of TRPC1 in the cortex were determined by Western blot and immunohistochemical staining. The results were compared with those in DMSO control group and normal group. The changes of neurons and myelin sheath were detected under electron microscope. The apoptosis of cortical neurons was detected by TUNEL. One-way ANOVA was used to compare within each group.Results The protein expressions of TRPC1 in the cortex increased after DAI and reached the peak at day 1 and then gradually decreased while intracellular calcium concentration also reached the peak at day 1. The structure of myelin sheath was destructed at the same time. After injection of TRPC1 blocker SKF96365, the protein expression of TRPC1 was inhibited and intracellular calcium concentration decreased. Meanwhile, the structure of myelin sheath was partially reserved and the scores of neurological functions in rats were improved. Conclusion TRPC1-induced calcium overload after DAI is the major cause of myelin degeneration and neuronal death. Suppressing the calcium influx induced by TRPC1 can protect the normal structure of myelin and improve neuronal apoptosis. [ABSTRACT FROM AUTHOR]