藏药七十味珍珠丸对帕金森病模型大鼠认知能力的影响OA北大核心CSTPCD

AIM:To investigate the effect of Tibetan medicine Ranasampel(RNSP)on the cognitive ability of Parkinson disease(PD)model rats.METHODS:The PD rats were established by 6-hydroxydopamine(6-OHDA)single-point injection in right striatum.The animals were randomly divided into PD model group,Medopar group(Medopar 50 mg/kg),RNSP low-dose,medium-dose,high-dose group(90,180,360 mg/kg)and normal group,with 8 rats in each group.The rats in each group were intragastrically administered once a day for 4 weeks after modeling,while the PD mod-el group and normal group received equal volume of saline.The rats were weighed on first day of RNSP administration,then on the 7th,14th,21th and 28th days.After 4 weeks of RNSP administration,apomorphine induced Rotation experi-ment and the Morris water maze experiment were performed.The number of tyrosine hydroxylase(TH)positive neurons in the substantia nigra densities(SNc)and ventral tegmental area(VTA)of the midbrain was observed by immunohistochem-istry.The levels of malonaldehyde,reduced glutathione and superoxide dismutase in the striatum of rats were measured by enzyme-linked immunosorbent assay.The levels of dopamine,5-hydroxytryptamine and noradrenaline in hippocampus of rats were detected by high performance liquid chromatography electrochemical method.The protein expressions of P38,p-P38,JNK,p-JNK,ERK and p-ERK in the substantia nigra of rats were detected by Western blot.RESULTS:After 4 weeks of RNSP administration,there was no significant different in body weight among the groups.Compared with normal group,the rotation frequency of the PD model group was increased significantly,the escape latency was significantly pro-longed,the number of table crossing times and the target-zone duration time were significantly decreased(P<0.05 or P<0.01).The number of TH positive neurons were significantly reduced in SNc and VTA;The levels of reduce glutathione and superoxide dismutase in the striatum were significantly decreased,and the level of malondialdehyde was significantly increased(P<0.05).The levels of dopamine,5-hydroxytryptamine and norepinephrine in the hippocampus were de-creased;The ratios of p-JNK/JNK and p-P38/P38 in the substantia nigra were significantly increased(P<0.05).Com-pared with PD model group,the rotation frequency of the RNSP groups was significantly decreased,the escape latency was significantly shortened,and the number of table crossing times and target-zone duration time were significantly increased(P<0.05).The number of TH-positive neurons,and the levels of reduced glutathione,superoxide dismutase,and dopa-mine were significantly increased,while the level of malondialdehyde and the ratios of p-JNK/JNK and p-P38/P38 were sig-nificantly decreased(P<0.05).The noradrenaline level in the medium and high dose groups and the 5-hydroxytryptamine level in the low and high dose groups were significantly increased,and the ratio of p-ERK/ERK in the medium and high dose groups were significantly decreased(P<0.05).CONCLUSION:RNSP can improve the cognitive ability of PD mod-el rats,and the mechanism may be related to inhibiting the P38/JNK/ERK signaling pathway,reducing the oxidative stress response in the midbrain,reducing the loss of DA neurons,and improving the monoamine neurotransmitters in the hippo-campus.