Triptolide improves spinal cord injury recovery via upregulation of autophagy and inhibition of apoptosis in Thy-YFP transgenic mice

doi:10.3969/j.issn.2095-4344.2886

Abstract

Abstract:

BACKGROUND: Studies have shown that treatment with triptolide reduces ischemic lesion area, water

content, and nerve cell death in a rat model of stroke. In addition, triptolide can promote the repair of spinal cord injury by inhibiting astrocyte hyperplasia, microglia activation and inflammatory response.

OBJECTIVE: To investigate the effect of triptolide on the autophagy and apoptosis in the spinal cord of Thy-YFP transgenic mice after spinal cord injury.

METHODS: Sixty Thy-YFP transgenic mice were randomly divided into four groups: sham, dimethyl sulfoxide (DMSO), triptolide and methylprednisolone groups. Following the establishment of the spinal cord injury models, mice in the triptolide, DMSO and sham group were immediately intraperitoneally injected with triptolide (0.2 mg/kg·d) or 5% DMSO-normal saline solution (0.2 mg/kg·d) for 7 days, whereas mice in the methylprednisolone group were intraperitoneally injected with methylprednisolone (30 mg/kg) at 30 minutes, 6 hours and 24 hours after surgery. Basso Mouse Scale was used to assess the recovery of motor function; hematoxylin-eosin staining and Nissl staining were used to explore tissue recovery after spinal cord injury; western blot and immunofluorescence staining were employed to assess the levels of autophagy-associated proteins, Beclin-1, LC3B, p62, and apoptosis-associated proteins, Bcl-2, Bax and caspase-3. An ethic approval for animal experiments was obtained from Hebei North University with an approval No. W20200002.

RESULTS AND CONCLUSION: Treatments with triptolide or methylprednisolone after spinal cord injury significantly improved motor function and reduced neuronal cell death. In addition, the expression of autophagy-associated protein LC3B was upregulated and the expression of p62 was downregulated following triptolide treatment; the expressions of apoptosis-associated proteins caspase-3 and Bax were reduced, while the expression of anti-apoptosis protein Bcl-2 was increased after triptolide treatment. To conclude, triptolide improves the motor function after spinal cord injury, which is related to upregulation of autophagy and inhibition of apoptosis. Triptolide may be a potential neuroprotective agent for spinal cord injury.

Key words: triptolide, autophagy, apoptosis, spinal cord injury, animal, mouse, experiment

CLC Number:

Zhu Ning, Yang Xinming, Ruan Jianwei. Triptolide improves spinal cord injury recovery via upregulation of autophagy and inhibition of apoptosis in Thy-YFP transgenic mice[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(35): 5650-5655.

Figures/Tables 6

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