Intervention And Its Molecular Mechanism Of SREBP And PPAR In SO₂Treated Rats And The Diabetic Rats

Diabetes and other metabolic disorders syndrome are gradually becoming a major metabolic diseases that endanger human health. Substantial evidence that there is a significant correlation between metabolic diseases and air pollution, SO2is one of the reasons. This subject built diabetic rat model using streptozotocin (STZ) to conduct SO2-acting inhalation exposure and drug intervention using Sterol-regulatory element binding proteins (SREBP) inhibitor Betulin and peroxisome proliferator-activated receptor (PPAR) agonists Thiazolidinedione (TZD). Research their effect on key mRNA expression. Analysis of body weight, glucose and lipid metabolism-related biochemical changes to reveal drug intervention and its molecular mechanisms in mice and diabetic rats.The experimental animals were divided into control group, SO2group, model group, the SO2+model group, SO2+TZD group, SO2+Betulin group, model+TZD group and model+Betulin group. Conducted exposure treatment to Wistar rats of SO2group with14.0mg/m3SO24h per day in30days. Drug intervention therapy was adoped for Wistar rats of drug intervention group in30days. Rats of control group were exposed in the same box to accept the same time filtered fresh air. Body weight, blood glucose, glycosylated hemoglobin, free fatty acids, triglycerides,insulin,liver glycogen,muscle glycogen and high-low-density cholesterol and other biochemical indicators were detected. Results showed that SO2can disrupt the normal glucose metabolism, the mechanism may be related to the destruction of the pancreatic beta cell function and increase in gluconeogenesis. On the other hand, SO2can cause lipid metabolism disorders, increase synthesis of free fatty acids, inhibit fatty acid oxidation, but no significant correlation with hyperlipidemia.SO2inhalation has no synergies with diabetes caused by STZ. TZD can’t improve glucose metabolism disorder caused by SO2, showing that PPAR is not the way metabolic disorders occurred by SO2. Betulin improved disorder of glucose metabolism caused by SO2obviously, indicating that SREBP participated in metabolic injury induced by SO2.Real-time PCR experimental results showed that Betulin has visible damage protective effect on key genes of SREBP and PPAR signaling pathways, and the intervention of PPAR was relatively weak, proving that SREBP played a key function on metabolic injury caused by SO2. The intervention to SREBP and PPAR signaling pathway was relatively weak, indicating that although key genes of the PPAR signaling pathway involved in the metabolic damage caused by SO2, but not by PPAR-mediated.