Mechanism of action of isorhynchophylline in attenuating dopaminergic neuronal damage in Parkinson's mice
Objective To investigate the effects of isorhynchophylline on dopaminergic neuronal damage and apoptosis in Parkin-son's(PD)mice and its possible mechanism of action.Methods From June 2020 to June 2022,forty micewere selected to establish the PD model,and the successful mice were assigned into model group,the low,medium and high dose of isorhynchophylline groups with 10 mice in each group according to the random number table method,and another 10 mice were selected as control group.The mice in the low,medium andhigh dose groups were given 20,40 and 80 mg/kg of isorhynchophylline suspension(prepared with 0.9%sodium chloride solution)by gavage,while the control and model groups were given equal amounts of 0.9%sodium chloride solution.The behavioral changes of mice in each group were evaluated by pole climbing test and open field test.The levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum and dopamine(DA)in brain were detected by ELISA.TUNEL method was used to detect neuronal apoptosis in substantia nigra.The mRNA relative expression levels of miR-376b-3p,transcription factor SP1(SP1)and leucine repeat sequence kinase 2(LRRK2)in the substantium nigra region were detected by reverse transcription quantitative poly-merase chain reaction(RT-qPCR).The expressions of SP1,LRRK2,α-synuclein(α-syn)and tyrosine hydroxylase(TH)in substantia nigra were detected by Western blotting.Results Compared with the control group(4.58±0.27)µg/L,the model group(1.35±0.13)µg/L showed a significant decrease in mouse DA levels(P<0.05).Compared with the model group,the low-dose group of isorhynchophyl-line(1.86±0.17)µg/L,the medium-dose group(2.56±0.21)µg/L,and the high-dose group(3.40±0.29)µg/L exhibited significant in-creases in mouse DA levels(all P<0.05),with the high-dose group of isorhynchophylline showing the best effect.Compared with the model group,the climbing time,IL-1β,TNF-α,neuronal apoptosis rate,the expression levels of SP1 and LRRK2 mRNA and protein,α-syn protein expression were decreased,the total distance of exercise,miR-376b-3p,TH protein level were increased of mice in the low,medium and high dose of isorhynchophylline groups(P<0.05),and the high dose of isorhynchophylline was the best(P<0.05).Con-clusion Isorhynchophylline can improve the behavioral dysfunction of PD mice to a certain extent,reduce the neuroinflammatory re-action,and reduce the rate of neuronal apoptosis,which may play a role by affecting miR-376b-3p/SP1/LRRK2 signal system.
万方数据
维普
