目的 探究黃芩素對(duì)創(chuàng)傷性腦損傷大鼠血腦屏障和神經(jīng)元焦亡的影響及對(duì)NOD樣受體熱蛋白結(jié)構(gòu)域3（NLRP3）/半胱天冬酶-1（Caspase-1）信號(hào)通路的影響。方法 將大鼠隨機(jī)分為對(duì)照組、模型組、黃芩素（2.5、5.0、10.0 mg/kg）組，每組12只。黃芩素組分別按2.5、5.0、10.0 mg/kg劑量ip黃芩素。ELISA法測(cè)定大鼠血清腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素（IL）-6、谷胱甘肽過氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平；伊文思藍(lán)（EB）染料的超流體測(cè)量血腦屏障的通透性；TUNEL和Caspase-1雙染法檢測(cè)細(xì)胞焦亡情況；熒光定量PCR（RT-qPCR）測(cè)定大鼠腦海馬組織中閉鎖小帶蛋白1（ZO-1）、緊密連接蛋白1（Claudin-1）、閉合蛋白（Occludin）的mRNA表達(dá)量；Western blotting法檢測(cè)腦海馬組織中NLRP3/Caspase-1通路相關(guān)蛋白表達(dá)。結(jié)果 與模型組相比，黃芩素各劑量組大鼠病變半球EB含量顯著降低，血腦屏障通透性顯著改善，ZO-1、Claudin-1、Occludin mRNA及SOD、GSH-Px水平顯著上升（P＜0.05），海馬組織細(xì)胞焦亡率及MDA、IL-6、TNF-α、NLRP3、Caspase-1、GSDMD-N、IL-1β和IL-18水平顯著下降（P＜0.05）。結(jié)論 黃芩素可抑制NLRP3/Caspase-1信號(hào)通路，減輕炎癥反應(yīng)和氧化應(yīng)激反應(yīng)，改善創(chuàng)傷性腦損傷大鼠血腦屏障和神經(jīng)元焦亡。

Objective To investigate the impacts of baicalein on the blood-brain barrier and neuronal pyroptosis in rats with traumatic brain injury, and its impact on the NLRP3/Caspase-1 signaling pathway. Methods Rats were assigned into control group, model group, baicalein (2.5, 5.0, and 10.0 mg/kg) group, with 12 rats in each group. Baicalein groups were intraperitoneally injected with baicalein at doses of 2.5, 5.0, and 10.0 mg/kg, respectively. The serum TNF-α, IL-6, GSH-Px, SOD, and MDA were determined by ELISA method. The superfluid of Evans blue (EB) dye was used to measure the permeability of the blood-brain barrier. TUNEL and Caspase-1 double staining method was applied to detect cell apoptosis. RT-qPCR was applied to measure the mRNA expression levels of ZO-1, Claudin-1, and Occludin in hippocampal tissue. The expression of NLRP3/Caspase-1 pathway related proteins in hippocampal tissue were detected by Western blotting. Results Compared with the model group, the EB content in the affected hemisphere of rats in the baicalein groups were greatly reduced, and the permeability of the blood-brain barrier was greatly improved, the levels of ZO-1, Claudin-1, Occludin mRNA, and SOD and GSH-Px were greatly increased (P < 0.05), the cell apoptosis rate and the levels of MDA, IL-6, TNF-α, NLRP3, Caspase-1, GSDMD-N, IL-1β, and IL-18 were greatly decreased (P < 0.05). Conclusion Baicalein can inhibit the NLRP3/Caspase-1 signaling pathway, alleviate inflammatory and oxidative stress responses, and improve the blood-brain barrier and neuronal pyroptosis in traumatic brain injury rats.

R285.5

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃(聯(lián)合共建)項(xiàng)目(LHGJ20191175)