Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Tác động của các tác nhân nhiễm trùng đối với phản ứng viêm toàn thân và tổn thương sinh lý trong mô hình thử nghiệm tiền lâm sàng ở linh trưởng không người và chấn thương đa dị
Tóm tắt
Các mô hình chấn thương động vật hiện có còn hạn chế trong việc tái hiện sinh lý bệnh của chấn thương do tai nạn ở người. Trong nghiên cứu này, chúng tôi đã mô tả ảnh hưởng sinh lý và phản ứng viêm trong hai mô hình chấn thương ở linh trưởng không người có tính lâm sàng cao. Các khỉ Macaque Cynomolgus ở Mauritius đã trải qua một trong hai loại chấn thương: tổn thương gan do phẫu thuật nội soi vùng bụng kín (cắt gan 60% thùy trái) trong mô hình chấn thương mất máu không kiểm soát (THM) hoặc mô hình chấn thương đa ngã kết hợp (PHM) liên quan đến tổn thương gan và ruột kết hợp, mất máu nặng không kiểm soát cũng như một vết thương da toàn bộ bề dày. Các chiến lược hồi sức thể tích cố định được sử dụng trong THM và hồi sức theo mục tiêu được sử dụng trong PHM. Toàn bộ các thông số huyết thanh và hóa học lâm sàng quan trọng, các chỉ số sinh học huyết thanh của viêm hệ thống, các thông số tưới máu mô, cũng như tình trạng sống sót được so sánh giữa hai mô hình trong suốt thời gian nghiên cứu hai tuần. Các NHP trong cả THM (n=7) và PHM (n=21) đều cho thấy tình trạng tưới máu mô kém (lactate đỉnh 6.3 ± 0.71 mmol/L) với tổn thương cơ quan (creatinine đỉnh 3.08 ± 0.69 mg/dL) từ tổn thương gan tương tự (cắt gan 60% thùy trái), mặc dù các NHP trong PHM có mất máu đáng kể hơn (68.1% ± 12.7% so với 34.3% ± 2.3%, p=0.02), số lượng tiểu cầu thấp hơn (59 ± 25 so với 205 ± 46 K/uL, p=0.03) và có xu hướng cao hơn về tỷ lệ tử vong (90.5% so với 33.3%, p=0.09). Phản ứng viêm là mạnh mẽ ở cả hai mô hình với các giá trị cytokine đỉnh (IL-6 > 6000 lần so với mức cơ bản) và giá trị bạch cầu (WBC 27 K/uL) thường xảy ra xung quanh t = 240 phút từ thời điểm xảy ra tổn thương gan. Một phản ứng viêm hệ thống mạnh mẽ hơn được ghi nhận trong PHM với sự tăng mạnh các giá trị đỉnh của IL-6 huyết thanh (7887 ± 2521 pg/mL so với 1076 ± 4833 pg/mL, p=0.02), IL-1ra (34,499 ± 5987 pg/mL so với 2511 ± 1228 pg/mL, p<0.00) và IL-10 (13,411 pg/mL ± 5598 pg/mL so với 617 pg/mL ± 252 pg/mL, p=0.03). Phân tích so sánh này cung cấp một góc nhìn dài hạn độc đáo về phản ứng viêm sau chấn thương trong hai mô hình lâm sàng liên quan và cho thấy rằng việc bổ sung các tác nhân nhiễm trùng vào tổn thương cơ quan đặc tăng cường cả tổn thương huyết học và phản ứng viêm.
Từ khóa
#chấn thương động vật #linh trưởng không người #phản ứng viêm #mô hình mô phỏng #tổn thương đa dịTài liệu tham khảo
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