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Saponin Panax quinquefolius ức chế sự vôi hóa tế bào cơ trơn mạch máu thông qua việc kích hoạt yếu tố hạt nhân-erythroid 2 liên quan đến yếu tố 2
Tóm tắt
Saponin Panax quinquefolius (PQS) là thành phần hoạt tính chính của Panax quinquefolius. Bằng chứng mới nổi cho thấy PQS có tác dụng tích cực đối với bệnh tim mạch. Tuy nhiên, vai trò và cơ chế của PQS trong sự vôi hóa mạch máu vẫn chưa rõ ràng. Nghiên cứu hiện tại đã điều tra tác động của PQS lên sự vôi hóa của tế bào cơ trơn mạch máu (VSMCs). Nghiên cứu đã sử dụng môi trường vôi hóa chứa 3 mM phosphate vô cơ (Pi) để gây ra sự vôi hóa tế bào VSMCs của chuột. Chúng tôi đã khảo sát tác động của PQS lên sự vôi hóa VSMCs bằng cách sử dụng hóa phẩm đỏ alizarin và các thử nghiệm hoạt độ phosphatase kiềm (ALP). Mức độ của các loại oxy phản ứng (ROS) trong tế bào và hoạt động phiên mã của yếu tố hạt nhân-erythroid 2 liên quan đến yếu tố 2 (Nrf2) đã được xác định. Các mức độ biểu hiện mRNA và protein của Nrf2, gen chống oxy hóa heme oxygenase-1 (HO-1), các dấu hiệu sinh xương, bao gồm yếu tố phiên mã liên quan đến runt 2 (Runx2) và protein hình xương 2 (BMP2), và protein liên kết ECH như Kelch-1 (Keap1) cũng đã được đo. Xử lý với Pi đã làm tăng đáng kể sự lắng đọng canxi nội bào và hoạt độ ALP, những điều này đã bị PQS ức chế theo cách phụ thuộc vào nồng độ. Trong quá trình vôi hóa VSMCs, PQS ức chế sự biểu hiện mRNA và protein của Runx2 và BMP2. Điều trị PQS đã giảm sản xuất ROS nội bào và tăng đáng kể hoạt động phiên mã của Nrf2 và sự biểu hiện của Nrf2 cùng gen chống oxy hóa mục tiêu HO-1. PQS đã ức chế sự biểu hiện protein của Keap1 do Pi gây ra, Keap1 là một chất ức chế nội sinh của Nrf2. Điều trị siRNA Keap1 đã làm tăng sự biểu hiện của Nrf2 và giảm biểu hiện của Runx2 trong sự hiện diện của Pi và PQS. Nhìn chung, những phát hiện này cho thấy PQS có thể ức chế hiệu quả sự vôi hóa VSMCs bằng cách cải thiện stress oxy hóa và điều chỉnh các gen sinh xương thông qua việc thúc đẩy sự biểu hiện của Nrf2.
Từ khóa
#PQS #sự vôi hóa #tế bào cơ trơn mạch máu #Nrf2 #stress oxy hóa #gen sinh xươngTài liệu tham khảo
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