基于环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路探讨桦木酸对糖尿病动脉粥样硬化大鼠主动脉内皮功能的调控作用OA

Objective:To investigate the effect of betulinic acid(BA)on aortic endothelial function in rats with diabetic atherosclerosis(DAS)and explore its potential mechanism based on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods:Ninety 4-week-old rats were randomly divided into a control group,a model group,a low-dose betulinic acid group(20 mg/kg),a high-dose betulinic acid group(100 mg/kg),and a high-dose betulinic acid+cGAMP group(100 mg/kg+200 μg),with 18 rats in each group.The DAS rat model was established by a single intraperitoneal injection of strep-tozotocin(STZ)combined with high-sugar and high-fat feeding.Fasting blood glucose(FBG)levels were measured using a blood glucose meter.ELISA was used to detect the serum levels of fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),endothelial nitric oxide synthase(eNOS),nitric oxide(NO),endothe-lin-1(ET-1),von Willebrand factor(vWF),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β).Additionally,serum levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were determined.Hematoxylin-eosin(HE)staining was performed to observe the morphological changes of rat aortic tissue.Vascular tension was measured using a biological signal acquisition analyzer.Western blot(WB)was used to detect the protein expression levels of in rat aortic tissue.Results:Compared with the control group,the model group showed aggravated aortic tissue damage,increased levels of plaque area,FBG,FINS,HOMA-IR,TC,TG,LDL-C,ET-1,vWF,IL-6,IL-1β,and TNF-α,as well as elevated pro-tein expression levels of cGAS and the p-STING/STING ratio(all P＜0.05).in contrast,the levels of HDL-C,maxi-mum vascular endothelial relaxation rate,eNOS,and NO were decreased(all P＜0.05).Compared with the model group,the low-dose and high-dose BA groups exhibited alleviated aortic tissue damage,reduced levels of plaque area,FBG,FINS,HOMA-IR,TC,TG,LDL-C,ET-1,vWF,IL-6,IL-1β,and TNF-α,and downregulated protein expression levels of cGAS and the p-STING/STING ratio v.meanwhile,the levels of HDL-C,maximum vascular endothelial re-laxation rate,eNOS,and NO were increased(all P＜0.05).However,cGAMP could reverse the therapeutic effect of BA on rats with diabetic atherosclerosis.Conclusion:Betulinic acid may improve the function of aortic endothelial cells in diabetic arteriosclerotic rats by inhibiting the cGAS-STING signaling pathway,regulating glucose and lipid metab-olism,and reducing the secretion of inflammatory factors.