Tác động của Natri Phenylbutyrate đối với sự thay đổi hành vi do Lipopolysaccharide gây ra thông qua việc giảm thiểu stress oxy hóa và chuỗi viêm thần kinh

Inflammation - Tập 39 - Trang 1441-1452 - 2016
Ashok Jangra1, Chandra Shaker Sriram1, Mangala Lahkar1,2
1Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, India
2Department of Pharmacology, Gauhati Medical College, Guwahati, India

Tóm tắt

Căng thẳng oxido-nitrosative, viêm thần kinh và mức giảm của các yếu tố thần kinh (neurotrophins) đều có liên quan đến bệnh lý của lo âu và trầm cảm. Một vài nghiên cứu gần đây đã tiết lộ vai trò của căng thẳng lưới nội chất (ER) trong bệnh lý của stress và trầm cảm. Mục tiêu của nghiên cứu hiện tại là điều tra khả năng bảo vệ thần kinh của natri phenylbutyrate (SPB), một chất ức chế căng thẳng ER đối với hành vi lo âu và trầm cảm được gây ra bởi lipopolysaccharide (LPS) ở chuột Swiss albino. Hành vi lo âu và trầm cảm được khởi phát bằng cách tiêm LPS (0,83 mg/kg; i.p.). Nhiều thử nghiệm hành vi đã được thực hiện để đánh giá hành vi lo âu và trầm cảm ở chuột. Kỹ thuật PCR thời gian thực được sử dụng để phát hiện và xác định mức biểu hiện của các dấu hiệu căng thẳng ER (protein điều hòa glucose 78 kDa (GRP78) và protein liên kết CCAAT/enhancer đồng nhất (CHOP)). Việc tiền điều trị bằng SPB đã cải thiện một cách đáng kể hành vi lo âu và trầm cảm do LPS gây ra, như được thể hiện qua kết quả của các chế độ hành vi. Căng thẳng oxy hóa do LPS gây ra đã được cải thiện bởi việc tiền điều trị SPB ở vùng hippocampus (HC) và vỏ não trước trán (PFC). Viêm thần kinh đã giảm đáng kể nhờ tiền điều trị SPB ở những con chuột được tiêm LPS, như việc giảm các cytokine viêm (IL-1β và TNF-α). Quan trọng hơn, việc tiêm LPS đã làm tăng đáng kể mức biểu hiện mRNA GRP78 trong HC, điều này gợi ý đến sự tham gia của phản ứng protein chưa gấp (UPR) trong những bất thường hành vi do LPS gây ra. Những kết quả này đã làm nổi bật khả năng bảo vệ thần kinh của SPB trong mô hình bệnh lý lo âu và trầm cảm do LPS gây ra, mà có thể một phần là do ức chế chuỗi căng thẳng oxy hóa - viêm thần kinh.

Từ khóa

#căng thẳng oxido-nitrosative #viêm thần kinh #yếu tố thần kinh #căng thẳng lưới nội chất #hành vi lo âu và trầm cảm #natri phenylbutyrate #lipopolysaccharide

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