1-甲基-4-苯基-1,2,3,6四氢吡啶诱导小鼠嗅觉障碍的实验研究

Experimental study on 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced olfactory dysfunction in mice

目的探讨1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)诱导帕金森(PD)病小鼠嗅觉障碍的机制研究。方法应用MPTP制备PD小鼠急性模型,腹腔注射MPTP(15 mg/kg),每2 h注射1次,共4次,对照组注射同等剂量的生理盐水。MPTP注射后5 d,进行嗅觉功能检测,检测双侧嗅球的重量,采用Western Blot检测嗅球炎性因子环氧合酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)蛋白表达。结果注射后5 d,两组左侧和右侧嗅球重量比较,差异无统计学意义(P>0.05);MPTP组嗅闻旧垫料时间短于对照组,嗅闻新垫料时间长于对照组[(143.80±9.56)s vs(167.30±9.98)s]、[(156.20±9.56)s vs(131.10±10.97)s],差异有统计学意义(P<0.05);MPTP组嗅球COX-2、iNOS蛋白表达高于对照组,差异有统计学意义(P<0.05)。结论MPTP诱导的PD小鼠急性模型能够导致小鼠嗅觉功能障碍,此作用机制可能与炎症反应有关。

Objective To investigate the effects of l-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP)on olfactory function in Parkinson’s disease(PD)acute mouse model.Methods MPTP was used to prepare an acute model of PD in mice.MPTP(15 mg/kg)was injected intraperitoneally,once every 2 h,for a total of 4 times.The control group was injected with the same dose of normal saline.Five days after MPTP injection,the olfactory function test was performed to detect the weight of the bilateral olfactory bulbs,and Western blot was used to detect the protein expression of the inflammatory factor cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)of the olfactory bulb.Results There was no statistically significant difference in the weight of the left and right olfactory bulbs between the two groups at 5 d after injection(P>0.05);The time to smell the old litter in the MPTP group was shorter than that of the control group,and the time to smell the new litter was longer than that in the control group[(143.80±9.56)s vs(167.30±9.98)s],[(156.20±9.56)s vs(131.10±10.97)s],the difference was statistically significant(P<0.05);The expressions of COX-2 and iNOS in the olfactory bulb of the MPTP group were both higher than those of the control group,the difference was statistically significant(P<0.05).Conclusion MPTP-induced acute PD mouse model can cause olfactory dysfunction in mice,and this mechanism of action may be related to inflammation.