目的 探討同仁牛黃清心丸對血管性認知障礙模型大鼠腦組織保護作用及對核苷酸結(jié)合寡聚化結(jié)構(gòu)域樣受體蛋白3（NLRP3）/半胱氨酸蛋白酶-1（Caspase-1）/白細胞介素-1β（IL-1β）信號通路調(diào)控的機制研究。方法 采用結(jié)扎雙側(cè)頸總動脈建立血管性認知障礙大鼠模型。大鼠隨機分為假手術(shù)組、模型組、尼莫地平組、同仁牛黃清心丸（0.6、1.2、2.4 g/kg）組。蘇木精-伊紅（HE）染色檢測模型大鼠大腦皮質(zhì)及海馬組織病理變化；鍍銀染色檢測模型大鼠腦組織中神經(jīng)原纖維纏結(jié)病理改變；免疫組化檢測腦組織中β-淀粉樣蛋白（Aβ）表達水平；ELISA檢測腦組織中腫瘤壞死因子-α（TNF-α）的水平；Western blotting檢測大鼠腦組織中NLRP3、Caspase1、IL-1β蛋白表達水平。結(jié)果 同仁牛黃清心丸能明顯改善模型大鼠大腦皮質(zhì)及海馬神經(jīng)元減少、神經(jīng)元變性、壞死等病理損傷；同仁牛黃清心丸能明顯改善模型大鼠腦組織中神經(jīng)元排列散亂、神經(jīng)原纖維增粗、銀染加深等病理改變。與模型組比較，同仁牛黃清心丸各劑量組能明顯降模型大鼠腦組織中Aβ、TNF-α、NLRP3、IL-1β表達水平（P＜0.05、0.01）；同仁牛黃清心丸0.6 g/kg組能明顯下調(diào)模型大鼠腦組織中Caspase1蛋白表達（P＜0.01）。結(jié)論 同仁牛黃清心丸對血管性認知障礙造成的腦組織損傷具有較好的改善作用。其中抑制NLRP3/Caspase1/IL-1β信號通路活化，改善神經(jīng)炎癥反應(yīng)可能是藥物發(fā)揮治療血管性認知障礙效應(yīng)機制的關(guān)鍵環(huán)節(jié)。

Objective To explore the protective effect of Tongren Niuhuang Qingxin Pills on brain tissue of vascular cognitive impairment model rats, and the mechanism of its effect on NLRP3/Caspase1/IL-1β signaling pathway regulation. Methods Establishing a vascular cognitive impairment rat model by ligating bilateral common carotid arteries. The rats were randomly divided into sham operation group, model group, Tongren Niuhuang Qingxin Pills (0.6, 1.2, and 2.4 g/kg) groups. Pathological changes in the cerebral cortex and hippocampus of model rats were detected by HE staining detection, pathological changes of neurofibrillary tangles in the brain tissue of model rats were detected by silver staining. Immunohistochemical detection of Aβ expression levels in brain tissue, ELISA detection of TNF-α levels in brain tissue; Western blotting was used to detect the expression levels of NLRP3, Caspase1, and IL-1β proteins in rat brain tissue. Results Tongren Niuhuang Qingxin Pills could significantly improve pathological damage such as neuronal reduction, degeneration, and necrosis in the cerebral cortex and hippocampus of model rats, Tongren Niuhuang Qingxin Pills could significantly improve the pathological changes in the brain tissue of model rats, such as disordered arrangement of neurons, thickened nerve fibers, and deepened silver staining. Compared to the model group, Tongren Niuhuang Qingxin Pills (0.6, 1.2, and 2.4 g/kg) group could significantly reduce the expression level of Aβ, TNF-α, NLRP3, IL-1β in the brain tissue (P < 0.05, 0.01). Tongren Niuhuang Qingxin Pills 0.6 g/kg group could significantly downregulate the expression of Caspase1 protein in the brain tissue (P < 0.01). Conclusion Tongren Niuhuangqingxin Pills had a good effect on brain tissue injury caused by vascular cognitive impairment. Among them, inhibiting the activation of the NLRP3/Caspase1/IL-1β signaling pathway to improve the neuroinflammatory response might be a key link in the drug's effect mechanism of treating vascular cognitive impairment.

R285.5;R286.1

北京市中醫(yī)藥科技發(fā)展資金項目（BJZYYB-2023-51）