Double Regulation of Supplement-Detoxification on Diabetic Atherosclerosis by Inhibiting Excessive Autophagy

Abstract

<i>Objecive</i> To explore the mechanism of Huoxue Jiedu Jiangtang recipe (HJJR) in regulating the hyperactivation of endoplasmic reticulum stress (ERS) autophagy PERK-eIF2a-LC3 pathway, and reveal its prevention for diabetic atherosclerosis. <i>Methods</i> First, the rats were injected with streptozotocin intraperitoneally to make the diabetic models, and then the aortic balloon injury combined with high-fat feeding were used to make the models of atherosclerosis who were randomly divided into model group, western medicine group (Gliquidone + Benazepril), low-dose HJJR group (HJJR₁), high-dose HJJR group (HJJR₂), and accepted corresponding drugs for 8 weeks respectively. Another blank group was used as control. The changes of serum glycosylated hemoglobin (GHb), homocysteine (Hcy) and angiotensinII (Ang1I) were compared. HE staining was used to detect aortic pathology. The mRNA transcription of PRK-like endoplasmic reticulum kinase (PERK), eucaryotic translation initation factor 2α (eIF2α) and CCAAT / Enhance-Binding Protein Homologous Protein (CHOP) were tested by reverse- transcription polymerase chain reaction (RT-PCR). Western blot were used to detect the expression of autophagy activating protein ATG6 (Beclin-1), autophagy protein microtubule-associated protein light chain LC3-1, LC3-II and LC3-II/LC3-I. <i>Results </i>Compared with the model group, after the drug intervention, the aortic tissue injury in each drug group were reduced, and the improvement in the Chinese medicine group was significantly better than that of the western medicine group (P < 0.05). All treatment groups could significantly lowed the levels of serum GHb, Hcy, and Ang1I (P < 0.05), could down regulate the transcription level of PERK, eIF2α and CHOP mRNA (P < 0.05); and decreased the amount of Beclin 1, LC3-II and LC3-II/LC3-1 autophagy protein in aortic cells (P < 0.05). The effect of HJJF group was better, and it was more significant with the increase of HJJF dose. <i>Conclusion</i> HJJR can protect arteries by inhibiting ERS caused by metabolic disorder in diabetes, correcting the homeostasis affecting ER, reducing the overreaction of PERK-eIF2-LC3, and alleviating autophagy effect.