Resolvin D1 giảm nhẹ phản ứng miễn dịch bẩm sinh ở mô hình chuột thí nghiệm chảy máu dưới nhện

Molecular Neurobiology - Tập 58 - Trang 1963-1977 - 2021
Guang-Jie Liu1, Tao Tao2, Xiang-Sheng Zhang1, Yue Lu1, Ling-Yun Wu1, Yong-Yue Gao1, Han Wang3, Hai-Bin Dai1, Yan Zhou1, Zong Zhuang1, Chun-Hua Hang1, Wei Li1
1Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
2Department of Neurosurgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
3Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), Nanjing, China

Tóm tắt

Viêm quá mức là nguyên nhân chính ảnh hưởng đến tổn thương não sớm (EBI) và liên quan đến những hậu quả tiêu cực hoặc thảm khốc của chảy máu dưới nhện (SAH). Resolvin D1 (RvD1) có tác động chống viêm và giải quyết mạnh mẽ đối với viêm cấp tính hoặc mãn tính có nguồn gốc khác nhau. Do đó, chúng tôi giả thuyết rằng RvD1 có thể làm giảm viêm quá mức trong EBI sau SAH. Do đó, chúng tôi đã tạo ra một mô hình SAH bằng cách thủng sợi và cho 3 liều RvD1 khác nhau (0.3, 0.6, và 1.2 nmol) sau SAH thí nghiệm. Chúng tôi đã đánh giá điểm số thần kinh, phù não và tính toàn vẹn của hàng rào máu não; bên cạnh đó, sự xâm nhập của bạch cầu trung tính, cái chết của tế bào thần kinh, và sự phân cực viêm pro-inflammatory của tế bào viêm được quan sát bằng phương pháp mô bệnh học hoặc nhuộm miễn dịch huỳnh quang, phương pháp western blot, và qPCR. Sau khi xác nhận hiệu quả của RvD1 trong SAH, chúng tôi đã cho dùng chất đối kháng đặc hiệu FPR2 Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4) 30 phút trước khi thiết lập SAH để quan sát xem hợp chất này có thể loại bỏ tác động chống viêm của RvD1 hay không. Tổng thể, kết quả của chúng tôi cho thấy RvD1 có tác động chống viêm mạnh mẽ và giảm rõ rệt sự xâm nhập của bạch cầu trung tính và sự kích hoạt viêm pro-inflammatory của tế bào viêm, dẫn đến cải thiện đáng kể chức năng thần kinh và phục hồi mô não. Sau khi thêm WRW4, các tác động chống viêm của RvD1 đã bị loại bỏ. Những kết quả này cho thấy RvD1 có thể tạo ra tác động chống viêm tốt và giảm bớt EBI, điều này gợi ý rằng RvD1 có thể là một lựa chọn điều trị mới cho tổn thương do SAH gây ra.

Từ khóa

#Resolvin D1 #chảy máu dưới nhện #viêm quá mức #tổn thương não sớm

Tài liệu tham khảo

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