新聞資訊
【文獻(xiàn)研讀】石杉堿甲通過抑制內(nèi)皮細(xì)胞焦亡改善自發(fā)性蛛網(wǎng)膜下腔出血后的神經(jīng)功能缺損
日期：
2024年06月03日 10:30
近期《Huperzine A ameliorates neurological deficits after spontaneous subarachnoid hemorrhage through endothelial cell pyroptosis inhibition》在 Acta Biochimica et Biophysica Sinica（生物化學(xué)與生物物理學(xué)報）發(fā)表。該研究由西湖大學(xué)醫(yī)學(xué)院附屬杭州市第一人民醫(yī)院神經(jīng)外科和體檢中心團隊完成。該研究表明，石杉堿甲注射液可抑制內(nèi)皮細(xì)胞焦亡、抗氧化應(yīng)激，改善蛛網(wǎng)膜下腔出血（SAH）后的早期腦損傷。
背景介紹
Subarachnoid hemorrhage (SAH) is a severe stroke type [1,2] mainly caused by aneurysm rupture and is characterized by high morbidity and mortality [3]. Additionally, survivors often have cognitive impairments affecting patients’ daily functionality, labor capacity, and quality of life [4]. Early brain injury within 72 h is considered to be the main cause of poor prognosis in SAH patients [5]. Alleviating early brain damage contributes to the improvement on survival rate and prognosis of SAH patients [6,7]. Therefore, inhibiting early brain damage in SAH patients is an important therapeutic strategy for improving the prognosis of SAH patients. It has been revealed that neuronal apoptosis and blood-brain barrier (BBB) destruction are the hallmark events of early brain injury after SAH, are closely related to irreversible acute brain injury after SAH, and are important factors for poor prognosis in SAH patients [8,9]. In addition, the increased permeability of the BBB allows immune molecules to migrate to the brain parenchyma, which further exacerbates brain injury. It is suggested that inhibiting BBB dysfunction can effectively ameliorate early brain injury after SAH and is an important therapeutic method for improving the prognosis of SAH patients.
蛛網(wǎng)膜下腔出血（SAH）是一種嚴(yán)重的腦卒中類型[1,2]，主要由顱內(nèi)動脈瘤破裂引起，其特點是高致殘率和高死亡率[3]。此外，幸存者通常存在認(rèn)知障礙，影響患者的日常功能、勞動能力和生活質(zhì)量[4]。SAH后72 小時內(nèi)的早期腦損傷被認(rèn)為是影響SAH 患者預(yù)后不良的主要原因之一[5]。減輕早期腦損傷有助于改善 SAH 患者的生存率和預(yù)后[6,7]。因此，抑制 SAH 患者早期腦損傷是改善 SAH 患者預(yù)后的重要治療策略。研究表明，神經(jīng)元凋亡和血腦屏障（BBB）破壞是 SAH后早期腦損傷的標(biāo)志性事件，與 SAH后不可逆的急性腦損傷密切相關(guān)，是 SAH 患者預(yù)后不良的重要因素[8,9]。此外，血腦屏障的通透性增加使免疫分子遷移到腦實質(zhì)，這進(jìn)一步加劇了腦損傷。研究表明，抑制血腦屏障功能障礙可有效改善 SAH后的早期腦損傷，是改善 SAH 患者預(yù)后的重要方法。
材料和方法
Animal handling
SPF male SD rats were fed according to standard animal care proposal. After one week of adaptive feeding, the following treatments were carried out: (1) sham group: SD rats were subjected to a sham operation; (2) model group: SD rats were treated for SAH, and saline was applied intraperitoneally; and (3) treatment group: SD rats were treated for SAH, and Huperzine A (0.1 mg/kg, WEPON, Drug Approval Number: H20183340) was applied intraperitoneally. The procedure was as follows: after the SD rats were anesthetized, 0.35 mL of fresh autologous blood (20 s) without heparin was slowly injected into the anterior cistern of the optic chiasm, and the animals were kept head down at 30℃ for 20 min. The rats were immediately injected with 2 mL of normal saline and returned to the cage alone. The body temperature was maintained at 37°C. In the sham group, the SD rats (male, 250 -300 g) were injected with normal saline instead of autologous blood; in the model group and treatment group, the placebo (saline) and Huperzine A were administered intraperitoneally 12 h after autologous blood injection.
SPF 雄性 SD 大鼠按照標(biāo)準(zhǔn)動物飼養(yǎng)方案進(jìn)行飼養(yǎng)。適應(yīng)性飼養(yǎng)一周后，進(jìn)行以下處理：（1）假手術(shù)組：SD 大鼠進(jìn)行假手術(shù)操作；（2）模型組：SD 大鼠誘導(dǎo)蛛網(wǎng)膜下腔出血（SAH），腹腔注射生理鹽水；（3）治療組：SD 大鼠誘導(dǎo) SAH， 腹腔注射石杉堿甲（0.1 mg/kg，萬邦德制藥集團有限公司，藥品批準(zhǔn)號：H20183340）。操作步驟如 下：SD 大鼠麻醉后，緩慢注入不含肝素的新鮮自體血（20 s，0.35 mL）至視交叉前池，將動物頭向下保持在 30°C 下20 分鐘。立即注射2 mL生理鹽水， 將大鼠單獨放回籠中，體溫維持在 37°C。假手術(shù)組中，SD大鼠（雄性，250-300 g）注射生理鹽水代替自體血。在模型組和治療組中，大鼠自體血注射后 12 小時分別經(jīng)腹腔注射安慰劑（生理鹽水）和石杉堿甲。
研究結(jié)果
一、石杉堿甲改善 SAH 大鼠神經(jīng)功能缺陷和腦組織神經(jīng)元凋亡。
二、石杉堿甲通過改善 SAH 大鼠緊密連接蛋白的表達(dá)來抑制 BBB 功能障礙。
三、石杉堿甲改善了 SAH 大鼠腦組織內(nèi)皮細(xì)胞的焦亡。
四、石杉堿甲改善了 SAH 大鼠腦組織的氧化應(yīng)激，抑制了氧化應(yīng)激介導(dǎo)的內(nèi)皮細(xì)胞焦亡。
五、石杉堿甲抑制 SAH 大鼠腦組織內(nèi)皮細(xì)胞 NF-κB 通路的激活。
結(jié)論：植物單體石杉堿甲在肥胖相關(guān)的認(rèn)知障礙[32]、阿爾茨海默病和其他形式的癡呆[33]以及重復(fù)性創(chuàng)傷性腦損傷[34]中起神經(jīng)保護作用。在這項研究中，我們發(fā)現(xiàn)石杉堿甲可以顯著改善 SAH 大鼠的神經(jīng)功能缺損評分和平衡評分。據(jù)報道，石杉堿甲對神經(jīng)損傷的改善作用與其對神經(jīng)元凋亡的抑制作用有關(guān)[17,18]。在這項研究中，我們發(fā)現(xiàn)石杉堿甲可以顯著降低腦組織中神經(jīng)元凋亡的水平。我們的結(jié)果表明，石杉堿甲可以抑制神經(jīng)細(xì)胞凋亡，改善 SAH 后的早期神經(jīng)功能缺損。石杉堿甲已在多項臨床研究中被證明是安全的。本研究補充了石杉堿甲在神經(jīng)損傷疾病中的神經(jīng)保護功能，為 SAH 后早期腦損傷提供了新的潛在療法。
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聲明：
1.本新聞旨在分享學(xué)術(shù)前沿動態(tài)，僅供醫(yī)療衛(wèi)生專業(yè)人士基于學(xué)術(shù)目的參閱，非廣告用途。
2.萬邦德制藥不對任何藥品和/或適應(yīng)癥作推薦。
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