Bilobalide inhibits 6-OHDA-induced activation of NF-κB and loss of dopaminergic neurons in rat substantia nigra  

作　　者：Ling-yun LI Xi-lin ZHAO Xi-feng FEI Zhen-lun GU Zheng-hong QIN Zhong-qin LIANG 

机构地区：[1]Department of Pharmacology, Soochow University School of Medicine, Laboratory of Aging and Nervous Diseases, Soochow UniversitySchool of Medicine, Suzhou 215123, China

出　　处：《Acta Pharmacologica Sinica》2008年第5期539-547,共9页中国药理学报（英文版）

基　　金：Iproject supported by grants from the National Natural Science Foundation of China （No 30672452）, the Natural Science Foundation of Jiangsu Province （No BK2006051）, and the Natural Science Foundation of Jiangsu High Education Bureau （No 05KJB310117）.

摘　　要：Aim： To investigate the effects of bilobalide on the activation of NF-κB, and apoptosis of dopaminergic neurons induced by 6-hydroxydopamine （6-OHDA）. Methods： A rat model of Parkinson＇ s disease was produced with a unilateral infusion of 6-OHDA （8μg） into the substantia nigra par compact. Bilobalide was administered 5, 10, and 20 mg/kg （ip） once a day for 7 d, starting 6 d prior to the 6- OHDA infusion. The rats were subjected to locomotor activity and rotational behavior testing 2 or 3 weeks after the 6-OHDA infusion. The expressions of tyrosine hydroxylase （TH） and NF-κB p65 were examined by immunofluorescence. The loss of dopaminergic neurons was detected by Nissl＇s staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to identify apoptosis. Results： The behavioral changes due to 6-OHDA were significantly restored by bilobalide pretreatment. Bilobalide inhibited the 6-OHDA- induced loss of TH-positive neurons, decreased the activation of NF-κB, and protected dopaminergic neurons from apoptosis remarkably. Conclusion： NF-κB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-κB pathway is likely to be involved in the neuroprotective effect of bilobalide.Aim： To investigate the effects of bilobalide on the activation of NF-κB, and apoptosis of dopaminergic neurons induced by 6-hydroxydopamine （6-OHDA）. Methods： A rat model of Parkinson＇ s disease was produced with a unilateral infusion of 6-OHDA （8μg） into the substantia nigra par compact. Bilobalide was administered 5, 10, and 20 mg/kg （ip） once a day for 7 d, starting 6 d prior to the 6- OHDA infusion. The rats were subjected to locomotor activity and rotational behavior testing 2 or 3 weeks after the 6-OHDA infusion. The expressions of tyrosine hydroxylase （TH） and NF-κB p65 were examined by immunofluorescence. The loss of dopaminergic neurons was detected by Nissl＇s staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to identify apoptosis. Results： The behavioral changes due to 6-OHDA were significantly restored by bilobalide pretreatment. Bilobalide inhibited the 6-OHDA- induced loss of TH-positive neurons, decreased the activation of NF-κB, and protected dopaminergic neurons from apoptosis remarkably. Conclusion： NF-κB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-κB pathway is likely to be involved in the neuroprotective effect of bilobalide.

关 键 词：BILOBALIDE 6-HYDROXYDOPAMINE Parkinson＇sdisease NF-ΚB apoptosis 

分 类 号：R742.5[医药卫生—神经病学与精神病学]