To investigate the effects of curcumin on ferroptosis and neurological deficit in mice with intracerebral hemorrhage (ICH) and to clarify its potential molecular mechanism.
A total of 40 mice were divided into sham group, model group, experimental group and inhibitor group, with 10 mice in each group. Intracerebral hemorrhage model in mice was established by tail vein autologous blood injection. The sham group was injected with the same amount of normal saline; in the model group, the model group was established and injected with the same amount of normal saline; the experimental group was intragastrically administered with 200 mg·kg-1 curcumin, and the inhibitor group was intraperitoneally injected with 5 mg·kg-1 secretory phosphoprotein 1 (SPP1) inhibitor solution on the basis of 200 mg·kg-1 curcumin. At the end of the treatment, Longa score was used to evaluate the neurological deficit; the serum levels of Fe2+, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay (ELISA); the relative fluorescence intensity of reactive oxygen species (ROS) in brain tissue was detected by immunofluorescence method; the relative expression levels of B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein (Bax), nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPX4) were detected by Western blot; the relative positive level of SPP1 in brain tissue was detected by immunohistochemistry.
The neurological deficit scores of sham group, model group, experimental group and inhibitor group were (0±0), (3.20±0.42), (1.40±0.52) and (2.10±0.57) scores, respectively; the serum Fe2+levels were (220.35±26.17), (432.40±65.28), (276.52±33.20) and (329.15±45.71) μmol·kg-1, respectively; the serum MDA levels were (53.75±7.62), (120.36±18.22), (72.68±11.23) and (89.44±13.16) nmol·mg-1, respectively; the serum SOD levels were (63.78±9.80), (20.86±3.41), (51.18±7.30) and (37.35±5.08) U·mg-1, respectively; the relative fluorescence intensities of ROS were 1.00±0.09, 3.87±0.56, 1.52±0.22 and 2.43±0.38, respectively; the relative expression levels of Bax in brain tissue were 1.00±0.11, 2.95±0.33, 1.58±0.26 and 2.37±0.29, respectively; the relative expression levels of Bcl-2 were 1.00±0.15, 0.20±0.04, 0.65±0.12 and 0.43±0.07, respectively; the relative expression levels of Nrf2 were 1.00±0.13, 0.33±0.05, 0.65±0.10 and 0.54±0.09, respectively; the relative expression levels of GPX4 were 1.00±0.14, 0.21±0.04, 0.58±0.09 and 0.45±0.06, respectively; the relative positive levels of SPP1 were 1.00±0.13, 0.30±0.05, 0.76±0.12 and 0.43±0.07, respectively. There were statistically significant differences in the above indicators between the model group and the sham operation group, between the experimental group and the model group, and between the inhibitor group and the experimental group (P<0.05, P<0.01, P<0.001).
Curcumin can alleviate neuronal apoptosis and ferroptosis after ICH, and improve neurological function injury in mice. The underlying mechanism may be associated with the up-regulation of SPP1 expression, which in turn activates the Nrf2/GPX4 signaling pathway.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |