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天麻微注射抑制帕金森病大鼠中 6-OHDA 诱导的运动障碍:对 SNc 中氧化平衡和小胶质细胞激活的深入了解。

Gastrodin microinjection suppresses 6-OHDA-induced motor impairments in parkinsonian rats: insights into oxidative balance and microglial activation in SNc.

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

Herbal Medicine and Natural Product Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Inflammopharmacology. 2018 Oct;26(5):1305-1316. doi: 10.1007/s10787-018-0470-4. Epub 2018 Apr 3.

Abstract

PURPOSE OF THE RESEARCH

In this study, we appraised the effect of pre-treatment with intra-cerebro ventricular (i.c.v) microinjection of gastrodin (Gst) on catalepsy, motor imbalance, substantia nigra pars compacta (SNc) myeloperoxidase (MPO) activity, lipid peroxidation levels, nitric oxide (NO) production and total antioxidant capacity (TAC) in 6-hydroxydopamine (6-OHDA) rats model of PD.

MATERIALS AND METHODS

Male Wistar rats were pre-treated with i.c.v microinjections of Gst (20, 40 and 80 μg/3 μl/rat) for five consecutive days. Then, catalepsy and motor balance were induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat) into the SNc. The anti-cataleptic and motor balance improving effect of Gst was assessed by the Bar test and Rotarod 3 weeks after neurotoxin injection, respectively. SNc MPO activity and lipid peroxidation levels, NO production and TAC were assessed at the end of behavioral experiments.

RESULTS

Our data demonstrated that Gst pre-treatment significantly (p < 0.001) was prevented motor in-coordination and catalepsy in neurotoxin lesioned rats. The most motor improving effect was seen at 80 μg Gst (p < 0.001). Pre-treatment of parkinsonian rats with Gst meaningfully (p < 0.001) was suppressed MPO activity, lipid peroxidation and NO production. Furthermore, the TAC level in the SNc was increased (p < 0.001) in Gst-microinjected rats about to the normal non-parkinsonian animals.

MAJOR CONCLUSIONS

In summary, pre-treatment with Gst abolished 6-OHDA-induced catalepsy and improved motor incoordination by decreasing: SNc MPO activity, lipid peroxidation levels and NO production, and restoring SNc levels of TAC to the levels of healthy rats.

摘要

研究目的

在这项研究中,我们评估了预先经脑室内(i.c.v)微量注射天麻素(Gst)对帕金森病(PD)6-羟多巴胺(6-OHDA)大鼠模型中僵住、运动失衡、黑质致密部(SNc)髓过氧化物酶(MPO)活性、脂质过氧化水平、一氧化氮(NO)产生和总抗氧化能力(TAC)的影响。

材料和方法

雄性 Wistar 大鼠连续 5 天经 i.c.v 微注射 Gst(20、40 和 80μg/3μl/大鼠)预处理。然后,通过将 6-OHDA(8μg/2μl/大鼠)单侧输注到 SNc 中诱导僵住和运动失衡。通过巴宾斯基测试和旋转棒测试分别在神经毒素注射 3 周后评估 Gst 的抗僵住和改善运动平衡作用。在行为实验结束时评估 SNc MPO 活性和脂质过氧化水平、NO 产生和 TAC。

结果

我们的数据表明,Gst 预处理可显著(p<0.001)预防神经毒素损伤大鼠的运动不协调和僵住。80μg Gst 表现出最强的运动改善作用(p<0.001)。帕金森大鼠预先用 Gst 处理可显著(p<0.001)抑制 MPO 活性、脂质过氧化和 NO 产生。此外,Gst 微注射大鼠的 SNc TAC 水平增加(p<0.001),接近正常非帕金森大鼠。

主要结论

总之,Gst 预处理可通过降低 SNc MPO 活性、脂质过氧化水平和 NO 产生,恢复 SNc 的 TAC 水平至健康大鼠的水平,消除 6-OHDA 诱导的僵住和改善运动失调。

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