Tác dụng chống viêm, chống oxy hóa và chống apoptosis của Metformin làm giảm độc tính thần kinh do ethanol trong mô hình động vật của rối loạn phổ rượu bào thai

Neurotoxicity Research - Tập 40 - Trang 605-613 - 2022
Maryam Sabzali1, Akram Eidi1, Mehdi Khaksari2, Hossein Khastar2
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

Tóm tắt

Việc tiếp xúc với rượu trong thời kỳ thai kỳ có những tác động lâu dài đến cấu trúc não, dẫn đến sự thiếu hụt chức năng trong nhiều khía cạnh của hành vi, bao gồm khả năng học tập và ghi nhớ. Suy giảm nhận thức thần kinh do rượu gây ra ở thế hệ con cái liên quan đến việc kích hoạt chuỗi phản ứng oxy hóa - viêm, tiếp theo là sự thoái hóa thần kinh theo chương trình tế bào (apoptosis) rộng rãi ở nhiều vùng não, chẳng hạn như hồi hải mã (hippocampus). Metformin là phương pháp điều trị hàng đầu cho bệnh nhân tiểu đường. Nó nhanh chóng vượt qua hàng rào máu-não (BBB) và có tác dụng chống oxy hóa, chống viêm, và bảo vệ thần kinh. Trong nghiên cứu này, chúng tôi đã đánh giá tác dụng bảo vệ của metformin đối với viêm thần kinh liên quan đến ethanol, cũng như sự apoptosis của tế bào thần kinh trong hồi hải mã của chuột đực trưởng thành trong mô hình động vật của rối loạn phổ rượu bào thai. Việc điều trị bằng dung dịch ethanol trong sữa (5,25 và 27,8 g/kg, tương ứng) được thực hiện qua đường thông dạ dày từ 2–10 ngày sau sinh. Để kiểm tra các đặc tính chống oxy hóa và chống viêm của metformin, một thử nghiệm ELISA đã được tiến hành để xác định nồng độ yếu tố hoại tử khối u-α (TNF-α) và các enzym chống oxy hóa. Nhuộm hóa mô miễn dịch đã được thực hiện để đánh giá sự biểu hiện của protein axit fibrillar glial (GFAP) và caspase-3 đã cắt. Dựa trên kết quả, metformin đã gây ra sự tăng đáng kể trong hoạt động của superoxide dismutase (SOD) (P < 0.05) và glutathione peroxidase (GSH-Px) (P < 0.01). Mặt khác, nó đã làm giảm nồng độ TNF-α và malondialdehyde, so với nhóm ethanol (P < 0.01). Trong nhóm metformin, đã có sự giảm apoptosis tế bào trong hồi hải mã, cũng như các tế bào dương tính với GFAP (P < 0.01). Tổng thể, tín hiệu apoptosis, được điều chỉnh bởi chuỗi phản ứng oxy hóa viêm, có thể bị ức chế bởi metformin trong não chuột trưởng thành theo mô hình động vật của rối loạn phổ rượu bào thai.

Từ khóa

#metformin #viêm thần kinh #độc tính thần kinh #hồi hải mã #rối loạn phổ rượu bào thai #apoptotic signaling

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