Stress lưới nội chất gây tăng sinh do lipocalin-2 tham gia vào các bất thường động mạch phổi liên quan đến bệnh Kawasaki

Springer Science and Business Media LLC - Tập 64 - Trang 1000-1012 - 2020
Zhaoling Shi1,2, Yue Yin2, Chen Li2, Hui Ding1, Nan Mu2, Yishi Wang2, Shanshan Jin2, Heng Ma2, Manling Liu2, Jie Zhou3
1Department of Pediatrics, Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China
2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an, China
3Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China

Tóm tắt

Các trường hợp lâm sàng đã báo cáo về những bất thường về cấu trúc và chức năng động mạch phổi ở bệnh nhân mắc bệnh Kawasaki (KD); tuy nhiên, cơ chế tiềm ẩn của những bất thường này vẫn chưa được làm rõ. Trong nghiên cứu này, một mô hình chuột mắc bệnh KD đã được thiết lập thông qua tiêm dịch chiết thành tế bào Lactobacillus casei (LCWE) qua đường phúc mạc. Kết quả cho thấy có những bất thường về chức năng và cấu trúc động mạch phổi ở chuột KD. Hơn nữa, sự căng thẳng lưới nội chất tăng sinh (stress ER) đã được quan sát ở các động mạch phổi của chuột KD. Đặc biệt, mức độ lipocalin-2 (Lcn 2), một yếu tố khởi động viêm, đã tăng đáng kể trong huyết tương và mô phổi của chuột KD; mức Lcn 2 gia tăng sau khi kích thích bằng LCWE có thể do các bạch cầu trung tính đa nhân (PMNs) gây ra. Tương ứng, trong các tế bào cơ trơn động mạch phổi (PASMCs) nuôi cấy, Lcn 2 đã tăng cường đáng kể sự phân cắt và định vị nhân của yếu tố phiên mã kích hoạt-6 (ATF6), tăng cường phiên mã của protein điều hòa glucose 78 (GRP78) và chất ức chế sự phát triển nhánh thần kinh (NOGO), và thúc đẩy sự tăng sinh của PASMCs. Tuy nhiên, các mức độ protein tương tự C/EBP (CHOP) và caspase 12 không tăng lên. Việc điều trị bằng acid 4-phenyl butyric (4-PBA, một chất ức chế đặc hiệu của stress ER) đã ức chế sự tăng sinh PASMCs do Lcn 2 gây ra và làm giảm những bất thường động mạch phổi cũng như phì đại thất phải, đồng thời giảm áp lực tâm thu thất phải ở chuột KD. Tóm lại, Lcn 2 đáng kể tạo điều kiện cho stress lưới nội chất tăng sinh ở PASMCs, có thể là nguyên nhân dẫn đến các bất thường động mạch phổi liên quan đến KD.

Từ khóa

#bệnh Kawasaki #bất thường động mạch phổi #stress lưới nội chất #lipocalin-2 #tăng sinh PASMCs

Tài liệu tham khảo

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