The effect and mechanism of roflumilast on traumatic brain injury in rats

doi:10.11958/20221943

Abstract

Abstract:

Objective To investigate the effect of roflumilast (RF) on traumatic brain injury (TBI) in rats and its possible mechanism. Methods A total of 36 rats were divided into three groups by random number table method: the sham group, the TBI group and the TBI+RF group, with 12 rats in each group. The TBI model of rat was established by modified Feeney free fall method. Rats in the TBI+RF group were intraperitoneally injected with RF solution immediately, 1 day and 2 day after modeling, while rats in the Sham group and the TBI group were given equal volume solvent. The modified neurological severity score (mNSS) was performed on day 1, day 2, day 3, day 7 and day 14 after modeling. At 3 days after surgery, the pathological changes of neurons and the number of dead neurons in the perifocal cortex of rats were observed by HE staining. The contents of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the injured cortex of rats were detected by ELISA, and the contents of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in the perifocal cortex of rats were detected by immunohistochemistry. Results There was no significant difference in mNSS within 3 days after modeling between the TBI+RF group and the TBI group, but mNSS decreased at 7 and 14 days in the TBI+RF group (P<0.05). Compared with the Sham group, the TBI group had loose brain structure around the lesion, significant interstitial edema and more dead neurons (P<0.05). Interstitial edema was still observed around the lesion in the TBI+RF group, but the percentage of dead neurons was decreased compared with that in the TBI group (P<0.05). Compared with the Sham group, the contents of IL-1β, IL-6, TNF-α and NLRP3 were increased in the TBI group (P<0.05). The contents of IL-1β, IL-6, TNF-α and NLRP3 were decreased after RF treatment (P<0.05). Conclusion Roflumilast alleviates traumatic brain injury in rats by reducing the level of inflammatory mediators in the early stage of TBI, thus playing a neuroprotective role.

Key words: brain injuries, traumatic, NLR family, pyrin domain-containing 3 protein, interleukin-6, interleukin-1beta, tumor necrosis factor-alpha, Roflumilast

CLC Number:

R651.15

Figures/Tables 5

References 20

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组别	建模后时间（d）
组别	1	2	3	7	14
Sham组	1.50±0.58	1.00±0.82	1.25±0.50	1.00±0.82	1.00±0.82
TBI组	13.75±0.96^a	13.50±1.00^a	12.75±1.50^a	11.50±0.58^a	9.25±0.96^a
TBI+RF组	14.00±0.82^a	13.75±0.50^a	12.50±0.58^a	10.00±0.82^ab	7.25±0.96^ab
F	319.696^＊＊	332.739^＊＊	182.735^＊＊	232.200^＊＊	88.900^＊＊

组别	建模后时间（d）
组别	1	2	3	7	14
Sham组	1.50±0.58	1.00±0.82	1.25±0.50	1.00±0.82	1.00±0.82
TBI组	13.75±0.96^a	13.50±1.00^a	12.75±1.50^a	11.50±0.58^a	9.25±0.96^a
TBI+RF组	14.00±0.82^a	13.75±0.50^a	12.50±0.58^a	10.00±0.82^ab	7.25±0.96^ab
F	319.696^＊＊	332.739^＊＊	182.735^＊＊	232.200^＊＊	88.900^＊＊

组别	IL-1β	IL-6	TNF-α
Sham组	0.138±0.006	0.329±0.031	1.008±0.031
TBI组	0.174±0.013^a	0.506±0.037^a	1.444±0.127^a
TBI+RF组	0.158±0.004^ab	0.443±0.024^ab	1.286±0.044^ab
F	19.081^＊＊	33.698^＊＊	30.813^＊＊

组别	IL-1β	IL-6	TNF-α
Sham组	0.138±0.006	0.329±0.031	1.008±0.031
TBI组	0.174±0.013^a	0.506±0.037^a	1.444±0.127^a
TBI+RF组	0.158±0.004^ab	0.443±0.024^ab	1.286±0.044^ab
F	19.081^＊＊	33.698^＊＊	30.813^＊＊

组别	死亡神经元（%）	NLRP3阳性表达AOD值
Sham组	23.430±0.933	0.035±0.002
TBI组	51.213±1.590^a	0.055±0.002^a
TBI+RF组	37.198±1.528^b	0.039±0.04^b
F	403.925^＊＊	57.907^＊＊