Ischemic stroke, characterized by the disturbance in the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. Yet, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for stroke’s devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and Lycium barbarum polysaccharides (LBP) on cortical neurons using an in vitro ischemic model. In this study, we demonstrated that administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, significantly inhibited the increase of intracellular Ca2+ in cultured cortical neurons subject to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival. The protective effects were further confirmed in neurons with high endogenous n-3 PUFAs which were isolated from fat-1 mice. Our study also found that treatment with LBP (50 mg/L) activated Trk B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis. Notably, combined treatment of n-3 PUFAs and LBP showed a synergic effect on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium influx and neurotrophic pathway. The results of the study suggest that n-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.

缺血性腦中風是指由於腦部突發性的供血不足，導致腦組織功能障礙甚至 壞死。由於缺血性腦中風具有極高的致死、致殘率，因而成為威脅全球健康的 重要的疾病之一。然而，現在卻缺乏針對缺血性腦中風的有效治療藥物。 最近聯合治療成為缺血性腦中風的推薦治療方案。在本課題中，我們利用 皮質神經元所造的離體缺血性腦中風細胞模型，研究聯合使用 omega-3 多不飽 和脂肪酸與枸杞多糖的神經保護作用。我們發現，DHA 作為 omega-3 多不飽和 脂肪酸的重要及主要成員，能夠減少神經元細胞經歷 OGD/R 損傷后細胞內鈣離 子的升高，從而促進細胞的存活。Fat-1 細胞由於轉入 fat-1 基因，能夠將 omega-6 轉化為 omega-3 多不飽和脂肪酸，因此其細胞內 omega-3 多不飽和脂 肪酸的含量比普通細胞型多。Fat-1 細胞也在 OGD/R 損傷后細胞內鈣離子水平 的降低上，得到了與 DHA 相似的結果。 同時，本課題還發現，經過 LBP（終濃度 50mg/L）處理的神經元，能夠提 高神經營養因子受體 Trk B 的表達，從而減少了細胞在經歷 OGD/R 損傷後所致 的凋亡。值得注意的是，聯合使用 omega-3 多不飽和脂肪酸和 LBP 在對神經元 的保護中起到了協同作用，可能是通過同時降低細胞鈣內流及調節神經營養因 子通路達成的。 本研究結果表明，聯合使用 OMEG-3 多不飽和脂肪酸與枸杞多糖為缺血性 腦中風的治療提供新思路。 關鍵字：DHA，枸杞多糖，fat-1，協同作用， OGD/R