Abstract: Objective To investigate the effects of ozone on the expression of endoplasmic reticulum stress associated protein in rats spinal cord neurons in vivo, and to explore the mechanism of endoplasmic reticulum stress in ozone-induced neurotoxicity. Methods A total of 24 healthy and clean SD rats were randomly divided into 3 groups, control group, high concentration group and low concentration group, with 8 rats in each group. The process of ozone entering the subarachnoid space through intervertebral disc and epidural treatment was simulated by injecting ozone into the built-in tube of rats. Rats in the control group were intrathecally catheterized without any medication, while rats in the 60 μg/mL ozone group and 30μg/mL ozone group were intrathecally administered 10 μL 60 μg/mL and 30 μg/mL oxygen-ozone respectively. Twenty-four hours after the injection, 3 rats in each group were sacrificed, and the lumbar spinal cords were collected to detect the protein expressions of GRP78, CHOP, Caspase-12 and Sig-1R with Western blotting. The gait scores of all rats were recorded before and after oxygen-ozone injection once a day for 12 days. Results Compared 山 东 大 学 学 报 (医 学 版)57卷3期 -温雪彬,等.内质网应激在医用臭氧导致的大鼠脊髓神经毒性机制中的作用 \=-with the control group, the experimental groups had significantly higher gait scores(P<0.05). The 60 μg/mL group had longer recovery time of hind limb motor function than the 30 μg/mL group. Compared with the control group, the experimental groups had significantly higher expressions of endoplasmic reticulum stress related protein GRP78, CHOP, Caspase-12 and Sig-1R(all P<0.05), and the 60μg/mL group showed higher expressions than the 30 μg/mL group(all P<0.05). Conclusion In vivo, both high and low concentration medical ozone can cause damage on rats’ motor function. The mechanism may be explained that a low concentration of medical ozone activates the apoptosis through CHOP pathway, while high concentration of medical ozone can activate apoptosis through both CHOP and Caspase-12 pathway.

Key words: Ozone, Endoplasmic reticulum stress, Apoptosis, Sigma-1 receptor, Spinal cord neurotoxicity, Rat