神经退行性病

    DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson’s disease
  • Figure 2|NBP ameliorates the rotenone-induced loss of DA neurons and expression of α-synuclein in the substantia nigra in a rat model of Parkinson’s disease.

    We examined the role of NBP in α-syn expression and dopaminergic neuron loss in the SN in a rotenone-induced rat model of PD by measuring α-syn expression using western blot and dopaminergic neuron loss by immunostaining for TH. Our results show that rotenone induced α-syn expression in the SN compared with that in control rats (P = 0.0003; Figure 2A and B). However, the expression of α-syn in the SN was decreased after NBP treatment (P = 0.0115; Figure 2A and B). In addition, TH immunostaining showed that the proportion of TH-positive neurons in the SN of rotenone-treated rats decreased compared with those in control rats (P < 0.0001; Figure 2C and D). NBP treatment effectively inhibited the rotenone-induced loss of TH-positive neurons (P < 0.0001; Figure 2C and D).


    Figure 3|NBP decreases the iron content in the substantia nigra and serum in the rotenone-induced rat model of Parkinson’s disease.

    To determine whether the loss of dopaminergic neurons in the rotenone-induced PD model was caused by iron overload, we examined the roles of NBP in iron deposition in the SN by Perls’ iron staining and by measuring serum iron content by ICP–MS. We found that rotenone caused significant iron deposition in the SN (P = 0.0002; Figure 3A and B), and treatment with NBP stopped the iron deposition in the SN in the rotenone-induced rat model of PD (P = 0.0006; Figure 3A and B). In addition, serum iron was significantly increased in the rat model of PD (P = 0.0024; Figure 3C), and treatment with NBP significantly reduced serum iron induced by rotenone in the rat model of PD (P = 0.0052; Figure 3C). 


    Figure 5|NBP reduces oxidative stress and mitochondrial damage and increases xCT and GPX4 expression in the substantia nigra in a rat model of Parkinson’s disease.

    To further investigate whether the neuroprotective effect of NBP in PD was mediated by a decrease of iron and subsequent reduction in oxidative stress, we tested the effect of NBP on MDA and GSH in the SN, mitochondrial structure, and antiferroptosis-related protein (xCT and GPX4) expression in the rotenone-induced rat model of PD. Our results show that MDA levels increased (P < 0.0001; Figure 5A) and GSH levels decreased (P = 0.0448; Figure 5A) after rotenone treatment. NBP inhibited the effects of rotenone on MDA (P < 0.0001; Figure 5A) and GSH (P = 0.0011; Figure 5B) levels. In addition, we observed the mitochondrial structure of the SN by transmission electron microscopy and discovered that the mitochondria shrank, the mitochondrial cristae were reduced, and the outer membrane was ruptured after rotenone exposure in the rat model of PD (Figure 5C). As expected, NBP administration alleviated rotenone-induced mitochondrial structural damage and cristae reduction (Figure 5C). Because the changes that we observed in the mitochondria were similar to the mitochondrial features observed in ferroptosis, we measured antiferroptosis-related protein expression after NBP treatment in the rat model of PD. GPX4 (P = 0.0005; Figure 5D and E) and xCT (P = 0.0002; Figure 5D and F) expressions were significantly decreased in the SN of rotenone-treated rats. Treatment with NBP reversed this effect (GPX4: P = 0.001; xCT: P = 0.0001; Figure 5D–F).


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  • 发布日期: 2022-06-17  浏览: 200
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