Song Chao, Gao Chao, Wang Zhenxin
Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Brain Sci. 2022 Apr 28;12(5):571. doi: 10.3390/brainsci12050571.
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood-brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.
(1) 背景：化疗诱导的认知障碍（CICI）在癌症患者中经常出现，会损害他们的生活质量。以葡萄籽为原料的原花青素已被证明具有抗炎和神经保护作用，但其在预防CICI方面的作用尚未得到研究。(2) 方法：成年雄性小鼠接受2.3mg/kg顺铂或生理盐水注射，共三个周期，每个周期包括连续五天注射，然后休息5天。在顺铂治疗前1小时给予原花青素或生理盐水。治疗结束后进行认知测试、明胶酶谱分析和血脑屏障（BBB）通透性测试。用SHSY5Y细胞的刺激上清液处理RAW264.7细胞。此外，检测高迁移率族蛋白B1（HMGB1）的表达和MMP-9的活性。(3) 结果：重复顺铂治疗增加了BBB通透性、MMP-9活性，损害了情境恐惧条件反射和新物体识别任务中的表现。MMP-9基因敲除可挽救认知障碍和顺铂诱导的SHSY5Y细胞中HMGB1的上调。HMGB1/TLR4/IP3K/AKT信号通路导致RAW264.7细胞中MMP-9活性增加。原花青素治疗可减弱MMP-9活性、BBB损伤和CICI。(4) 结论：结果表明，MMP-9激活和BBB破坏与CICI有关。原花青素可能有效减轻顺铂的有害影响。
