敲低黏膜相关淋巴组织淋巴瘤易位蛋白1对大鼠脊髓损伤炎症因子表达及神经功能的影响

Effects of knockdown of mucosa-associated lymphoid tissue lymphoma translocation protein 1 on the expression of inflammatory factors and neurological function in rats with spinal cord injury

目的 探讨黏膜相关淋巴组织淋巴瘤易位蛋白1(mucosa associated lymphoid tissue lymphoma translocation protein1,MALT1)对大鼠脊髓损伤(spinal cord injury,SCI)后神经炎症及神经功能恢复的影响。方法 选取96只SD(Sprague Dawley)大鼠,随机分成普通组及MALT1敲低组,普通组分为假手术组(n=24)、脊髓损伤组(SCI组)(n=24)。MALT1敲低组分为假手术组(n=12)、SCI组(n=12)、SCI注射慢病毒阴性对照组(SCI+NC组)(n=12)、SCI注射慢病毒MALT1敲除组(SCI+KD组)(n=12)。利用大鼠BBB(Basso、Beattie和Bresnahan,BBB)评分评估大鼠运动能力,苏木素-伊红(hematoxylin-eosin,HE)染色明确SCI程度,免疫蛋白质印迹法检测各组小鼠脊髓白细胞介素6(interleukin-6,IL-6)、白细胞介素10(interleukin-10,IL-10)、肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)和MALT1的表达。结果 与假手术组相比,SCI组大鼠MALT1表达、神经炎症指标均较高,而运动能力较差(均P<0.05)。在SCI+KD组大鼠中,MALT1敲低在造模后10~28d改善大鼠BBB评分,减轻神经损伤(P<0.05),炎症因子IL-1β、IL-6和TNF-α表达下降(均P<0.05),但不影响IL-10表达(P>0.05)。结论 MALT1敲低通过抑制SCI炎症因子表达,可改善脊髓功能恢复。

Objective To investigate the impact of mucosa-associated lymphoid tissue lymphoma translocation protein 1(MALT1)on neuroinflammation and neurological function recovery after spinal cord injury(SCI)in rats.Methods Ninety-six SD(Sprague Dawley)rats were randomly divided into a normal group and a MALT1 knockdown group.The normal group was further divided into a sham group(n=24)and a SCI group(n=24).The MALT1 knockdown group was equally subdivided into 4 groups(12 each):a sham group,a SCI group,a SCI group injected with lentivirus as negative control(SCI+NC group),and a SCI group injected with lentivirus-mediated MALT1 knockdown(SCI+KD group).The rats'motor ability was assessed using the BBB(Basso,Beattie and Bresnahan)score.The severity of SCI was determined by hematoxylin-eosin(HE)staining.Western blot analysis was performed to detect the expression of interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-alpha(TNF-α),and MALT1 in the spinal cords of rats in each group.Results Compared with the sham surgery group,the SCI group exhibited higher MALT1 expression and neuroinflammatory markers,as well as poorer motor ability(all P<0.05).In the SCI+KD group,MALT1 knockdown improved the BBB scores from 10 to 28 days post-modeling,reduced neurological damage(P<0.05),and decreased the expressions of inflammatory cytokines IL-1β,IL-6,and TNF-α(all P<0.05),but had no effect on IL-10 expression(P>0.05).Conclusions Knockdown of MALT1 improves spinal cord functional recovery by inhibiting the expression of neuroinflammatory factors in SCI.