类固醇在严重脑静脉血栓形成中的神经保护潜力：NLRP3 炎症小体抑制的实验和临床探索。
Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition.
机构信息
Department of Emergency, Xuanwu Hospital Capital Medical University, Beijing, China.
Neurology and Intracranial Hypertension & Cerebral Venous Disease Center, National Health Commission of China, Xuanwu Hospital, Capital Medical University, Beijing, China.
出版信息
CNS Neurosci Ther. 2024 Nov;30(11):e70125. doi: 10.1111/cns.70125.
BACKGROUND
NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.
METHODS
A total of 94 male Sprague-Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.
RESULTS
In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, p < 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, p < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, p < 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, p < 0.01), decreased on day 7 in rats (n = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, p < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, p < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (r = 0.4273, p = 0.0020; r = 0.4938, p = 0.0029) and mRS (r = 0.5349, p = 0.0125; r = 0.6213, p = 0.026), while CSF IL-6 correlated positively with mRS on admission (r = 0.5349, p = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), p < 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, p < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all p < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed.
CONCLUSION
Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation.
背景
NLRP3 炎性小体相关炎症可能在严重 CVT 的病理生理学中起重要作用。使用类固醇作为抗炎药来改善严重 CVT 的预后仍然存在争议。
方法
共使用 94 只雄性 Sprague-Dawley 大鼠。我们评估了大脑、血液和 CSF 中 NLRP3 炎性小体与严重 CVT 大鼠和/或患者严重程度之间的动态关系。我们还探讨了类固醇对 CVT 后动物和/或患者中 NLRP3 激活、神经损伤和 CSF 循环障碍的影响。
结果
在大鼠中，与假手术组相比，NLRP3 相关因子在第 1 天升高，在第 2 天达到峰值（NLRP3，假手术组：0.79±0.22；第 2 天：1.25±0.08，p<0.01；前 Caspase-1，假手术组：0.58±0.13，第 2 天：1.20±0.44，p<0.05；GSDMD，假手术组：0.94±0.22，第 2 天：1.72±0.46，p<0.05；前 IL-1β，假手术组：0.74±0.15，第 2 天：1.35±0.09，p<0.01），在第 7 天（每组 n=4）下降。血栓（假手术组：0.00±0.00，第 2 天：3.44±0.70，p<0.0001）、梗死面积（假手术组：0.00±0.00，第 2 天：11.99±6.26，p<0.01）和神经功能缺损出现类似的趋势。在 50 例患者中，血清 NLRP3 和 IL-6 水平与 NIHSS（r=0.4273，p=0.0020；r=0.4938，p=0.0029）和 mRS（r=0.5349，p=0.0125；r=0.6213，p=0.026）呈正相关，而 CSF IL-6 与入院时的 mRS 呈正相关（r=0.5349，p=0.0125）。与基线相比，NLRP3（0.36（0.36，0.36）vs.0.41（0.37，0.84），p<0.0001）和 IL-6 下降（4.06±1.48 vs.12.03±7.80，p<0.05），同时伴有严重 CVT 患者类固醇治疗后神经功能缺损和 CSF 循环改善（均 p<0.01），在出院和 3 个月随访时。未观察到与类固醇相关的不良反应。
结论
短期类固醇治疗可能通过抑制 NLRP3 炎性小体相关炎症来改善严重 CVT 的预后。
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