Eslami Abriz Aysan, Araghi Atefeh, Nemati Mahdieh, Taghavi Narmi Maryam, Ahmadi Mahdi, Abedini Fatemeh, Keyhanmanesh Rana, Ghiasi Fariba, Rahbarghazi Reza
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.
Adv Pharm Bull. 2024 Jul;14(2):412-418. doi: 10.34172/apb.2024.039. Epub 2024 Mar 20.
Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors.
D2M was induced in male Wistar rats using a single dose of streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/d until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment.
Data showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions ( =0.005) and reach near-to-control values ( =0.28; =0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (=0.303) and reduced P62 ( =0.0433; =0.096), leading to the completion of autophagy flux under diabetic conditions.
DHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.
在多种ω-3多不饱和脂肪酸类型中，二十二碳六烯酸（DHA）在不同细胞谱系的糖尿病条件下已显示出治疗特性。在此，我们以自噬调控因子为重点，研究了DHA对2型糖尿病（D2M）大鼠的抗糖尿病特性。
使用单剂量链脲佐菌素（STZ）和高脂饮食诱导雄性Wistar大鼠患D2M，持续8周。在第2周，糖尿病大鼠接受950 mg/kg/d的DHA，直至研究结束。之后，对大鼠实施安乐死，并对主动脉和心脏组织样本进行苏木精-伊红（H&E）染色，用于组织学评估。使用实时PCR分析测量心脏样本中黏附分子ICAM-1和VCAM-1的表达。通过蛋白质印迹法，测量D2M大鼠在DHA治疗前后BCLN1、LC3和P62的蛋白质水平。
数据显示，诱导D2M后，血管细胞和心肌细胞内出现细胞内脂质空泡，而DHA减少了细胞内脂质滴和炎症反应。DHA可降低糖尿病条件下ICAM-1升高的水平（P = 0.005），并达到接近对照值（P = 0.28；P = 0.033）。基于蛋白质印迹法，D2M使BCLN1和LC3-II/I比值略有增加，而不影响P62。DHA促进了LC3II/I比值（P = 0.303）并降低了P62（P = 0.0433；P = 0.096），导致糖尿病条件下自噬通量的完成。
DHA可能通过激活D2D大鼠的适应性自噬反应来降低心血管细胞的脂毒性。
