Butylphthalide On The MPTP Mouse Model Of Parkinson's Disease Substantia Nigra Dopaminergic Neurons In TH, DAT, P-JNK/JNK Expression

ObjectivesParkinson's disease (PD) is a common age-related neurodegenerative disease, mainly characterized by dopaminergic neurons loss and degeneration of the sexual. JNK signal transduction pathway is an important branch of MAPK pathway, which in the cell cycle, production, apoptosis and cell stress and other physiological and pathological processes play an important role. Current research evidence suggests that occurrence of Parkinson's disease JNK signal transduction pathway involved. Butylphthalide is a kind of cress from rapeseed in South China isolated the active ingredient, referred to as NBP, a hormone known as celery, Chinese Academy of Medical Sciences Peking Union Medical College Institute of Chinese synthetic raceme, from the 80's Start Feng Yipu leading the research begun by the pharmacological effects of NBP:to improve regional cerebral blood flow in ischemic region, increasing the number of capillary ischemia, ischemic cerebral blood flow increased to improve the ischemic brain energy metabolism, reduce infarct size, reduce the neurological damage and cerebral edema; can improve mitochondrial function, enhance the respiratory chain function, can improve mitochondrial energy pumps to increase anti-oxidation, anti-apoptosis and thus play; to increase global cerebral ischemia in striatal cells extracellular amino acids and dopamine content. The purpose of this experiment based on the role of JNK in the pathogenesis of PD to study the NBP on the MPTP-induced dopaminergic neurotoxicity is a protective effect. We choose butylphthalide preparation for MPTP C57BL/6 mouse model of Parkinson's disease, by immunohistochemical staining and detection of Parkinson's disease in mice westernblot dopaminergic neurons of TH, DAT, p-JNK/JNK expression to observe and analyze its clinical significance. Methods1,Animal group 30 C57BL/6 mice were divided into groups using a randomized complete the following 3 groups of 10 each. (1) normal control group (NS +vegetable oil):intraperitoneal injection of saline and MPTP groups 5 d, then injected with equal volume of vegetable oil treatment group 14d. (2) MPTP group (MPTP+ vegetable oil):The MPTP (30 mg/kg) intraperitoneally consecutive 5 d, and then switch to the treatment group with equal volume of vegetable oil injection 14 d. (3) NBP treated group (MPTP+NBP):first to MPTP (30 mg/kg) by intraperitoneal injection 5 d, then NBP (NBP 40 mg/kg) intraperitoneally 14 d. Each animal was killed on day 19 were fixed after the brain tissues embedded in paraffin, to take part in the substantia nigra slices by immunohistochemical staining; other side of the substantia nigra brain tissue extracted quickly placed in-80℃freezer with in westernblot.2,Model Preparation MPTP (30 mg/kg) intraperitoneally 5 d row [1], mice immediately after injection of gait limp, irritability, hair and tail erect reactions, about 5-10 min after the resumption of normal, that is, Preparation of success as a model.3,Immunohistochemical staining detected TH, DAT expression 4. Westernblot to detect p-JNK, JNK expressionResults1,With the normal control group, MPTP mice dopaminergic neurons in the TH-positive neurons and decreases the number (P<0.05); with MPTP compared, NBP treated mice substantia nigra dopaminergic neurons of TH-positive neurons increase (P <0.05), both were statistically significant.2,With the normal control group, MPTP mice nigrostriatal dopaminergic nerve fibers in the DAT positive nerve fibers were the number decreased (P<0.05); with MPTP compared, NBP treated mice nigra profile like the body of DAT-positive nerve fibers in the number of expression (P<0.05), both were statistically significant.3,The control group almost has no p-JNK expression, MPTP group showed p-JNK/JNK expression was significantly increased and expression than the normal control group strength, the two differences was statistically significant (P<0.05), NBP treated group p-JNK/JNK expression compared with MPTP group decreased, the two differences was statistically significant (P<0.05).ConclusionsButylphthalide increase Parkinsonian Mice nigral dopaminergic neurons TH, DAT expression reduce p-JNK expression, antagonistic JNK signal transduction pathway improve dopaminergic neuronal function, This butylphthalide may become treatment PD drugs clinical possibility provides experimental basis.