Comparison of triptolide and methylprednisolone in promoting the repair of spinal cord injury by regulating autophagy and apoptosis

doi:10.3877/cma.j.issn.2095-9141.2022.03.002

Abstract

Abstract:

Objective

To compare the mechanism of triptolide (TP) and methylprednisolone (MP) in regulating autophagy and apoptosis, and promoting the repair of spinal cord injury (SCI), so as to provide a theoretical basis and new selective drugs for new alternative drugs for clinical replacement of MP for SCI.

Methods

After establishing the SCI model, 60 THY-YFP transgenic mice were randomly divided into sham-operated group (Sham group), DMSO solution treatment group (DMSO group), MP experimental group and TP experimental group. Mice in TP experimental group, DMSO and Sham group were intraperitoneally injected with TP (0.002 mg/10 g), the same amount of 5% DMSO and 0.9% NaCl solution immediately after surgery, and had been continuously administrated for 7 d. Mice in MP experimental group were intraperitoneally injected with MP solution (0.3 mg/10 g) at 30 min, 6 h and 24 h after surgery. BMC was used to evaluate motor function, HE staining and Nissl staining were used to detect the histological changes of the spinal cord, Western blot and immunofluorescence staining were used to detect the levels of autophagy-related proteins (Beclin-1, LC3B, and p62) and apoptosis-related proteins (Bcl-2, Bax, and caspase-3).

Results

After TP intervention, the BMS motor function score of SCI mice gradually increased over time, the number of neurons increased, the autophagy-related protein, Beclin-1 and LC3B increased and p62 decreased, the apoptosis-related protein, caspase-3, Bax decreased and the anti-apoptotic protein Bcl-2 increased. Regardless of motor function evaluation, histological changes, enhanced autophagy and reduced apoptosis after SCI, TP experimental group was superior to DMSO group, but no significant difference was found between TP experimental group and MP experimental group (P>0.05).

Conclusion

TP can promote the recovery of spinal cord motor function after injury by up-regulating autophagy and inhibiting apoptosis in acute neck SCI, and has the same potential protective effect on SCI compared with MP.

Key words: Spinal cord injury, Triptolide, Methylprednisolone, Repair, Cell apoptosis

Yao Yao, Xinming Yang, Yakun Du, Ning Zhu, Yanlin Yin, Yongli Jia, Ying Zhang, Peinan Zhang, Ye Tian, Lixing Chen. Comparison of triptolide and methylprednisolone in promoting the repair of spinal cord injury by regulating autophagy and apoptosis[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2022, 08(03): 132-140.

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组别	只数	第1天	第3天	第7天	第14天	第30天	第60天	χ²值	P值
Sham组	6	9	9	9	9	9	9
DMSO组	6	0	0^a	0(0,1.00)^a	2(1.00,2.00)^a	3(2.75,3.00)^a	4(3.00,4.00)^a	29.241	<0.001
MP实验组	6	0	0(0,1.00)^a	2(1.00,2.00)^a	3(3.00,4.00)^a	4.5(4.00,5.00)^a	7(6.00,7.25)^a	29.806	<0.001
TP实验组	6	0	0(0,1.00)^a	1.5(1.00,2.00)^a	3(2.75,3.00)^a	4(3.75,4.25)^a	6(5.75,7.00)^a	29.806	<0.001
χ²值			17.480	19.154	20.887	20.281	20.638
P值			0.001	<0.001	<0.001	<0.001	<0.001

组别	只数	第1天	第3天	第7天	第14天	第30天	第60天	χ²值	P值
Sham组	6	9	9	9	9	9	9
DMSO组	6	0	0^a	0(0,1.00)^a	2(1.00,2.00)^a	3(2.75,3.00)^a	4(3.00,4.00)^a	29.241	<0.001
MP实验组	6	0	0(0,1.00)^a	2(1.00,2.00)^a	3(3.00,4.00)^a	4.5(4.00,5.00)^a	7(6.00,7.25)^a	29.806	<0.001
TP实验组	6	0	0(0,1.00)^a	1.5(1.00,2.00)^a	3(2.75,3.00)^a	4(3.75,4.25)^a	6(5.75,7.00)^a	29.806	<0.001
χ²值			17.480	19.154	20.887	20.281	20.638
P值			0.001	<0.001	<0.001	<0.001	<0.001

组别	只数	组织学表达
Sham组	6	40.67±3.33
DMSO组	6	16.83±1.47^a
MP实验组	6	27.33±2.73^ab
TP实验组	6	29.50±2.88^ab
F值		79.027
P值		<0.001

组别	只数	组织学表达
Sham组	6	40.67±3.33
DMSO组	6	16.83±1.47^a
MP实验组	6	27.33±2.73^ab
TP实验组	6	29.50±2.88^ab
F值		79.027
P值		<0.001

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