Protective effect of adeno-associated virus sense transfection of GDF11 on vascular injury in type 2 diabetic rats
10.19405/j.cnki.issn1000-1492.2024.05.013
- VernacularTitle:腺相关病毒感染GDF11对2型糖尿病大鼠血管损伤的保护作用
- Author:
Yuqin WANG
1
,
2
;
Shaoqing CAO
;
Zhangyu WANG
;
Chengsi LI
;
Jiangping YE
;
Gangjun ZONG
Author Information
1. 安徽医科大学无锡临床学院心血管内科,无锡 214000
2. 安徽医科大学第五临床医学院心血管内科,合肥 230000
- Keywords:
diabetes mellitus;
adeno-associated virus;
recombinant growth transforming factor 11;
vascular endothelial cell injury;
glycogen deposition;
streptozotocin
- From:
Acta Universitatis Medicinalis Anhui
2024;59(5):826-833
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of adeno-associated virus sense transfection up-regulating the expression level of the growth and differential factor 11 (GDF11) in vivo on aortic injury in type 2 diabetic mellitus rats (T2DM).Methods Nine-week-old male SD rats were randomly selected to establish a T2DM model by using high-sugar and high-fat chow plus small-dose streptozotocin (STZ) combined induction.Both normal rats and dia-betic model rats were randomly divided into five groups:blank control group (Control group) , negative virus con-trol group (NC group), GDF11 adeno-associated virus group (GDF11 group), diabetic group (DM group), and diabetic + GDF11 adeno-associated virus group (DM+GDF11 group) .After 8 weeks of feeding, the serum con-centrations of insulin (INS) , advanced glycosylation end products (AGES) , recombinant growth transforming fac-tor 11 (GDF11), total cholesterol (T-CHO), triglycerides (TG), low-density lipoproteins (LDL-C), high-densi-ty lipoproteins (HDL-C) , asymmetric dimethylarginine (ADMA) , and malondialdehyde (MDA) were assayed in the rats;periodic acid-schiff stain(PAS stain) was used to observe the sites of glycogen deposition, and hematoxy-lin-eosin staining (HE) was used to observe vascular damage.Scanning electron microscopy was used to observe the damage of vascular endothelial cells and vascular elastic fibers, and protein blotting and immunohistochemistry were used to detect the expression levels of vascular injury-related proteins.Protein blotting and immunohistochem-istry were used to detect the expression levels of vascular injury-related proteins.Results The biochemical inde-xes showed that the serum concentrations of AGES, T-CHO, TG, LDL-C and MDA were higher in the DM group than those in the Control group (P<0.05), the concentrations of INS, GDF11, HDL-C and ADMA were signifi-cantly lower than those in the Control group (P<0.05) , and the concentrations of AGES and HDL-C were not sig-nificantly lower in the DM+GDF11 group compared with the DM group (P<0.05) .HDL-C was not significantly different from the DM group, and several other data were improved (P<0.05) .Pathological staining suggested that PAS staining in the DM group suggested that glycogen particles deposited in the endothelium and subendotheli-um of the aorta, HE staining observed thickening of the aortic mesentery, endothelial cells and elastic fibers broke off in an irregular alignment, and electron microscopy observed endothelial damage in the vasculature and elastic fi-bers broke off in the DM group, and these changes attenuated in the DM+GDF11 group.Protein blotting and im-munohistochemistry indicated that the expression of endothelial cell-associated proteins decreased in the DM group (P<0.05) , and mesenchymal markers elevated in the DM group (P<0.05) , these proteins were regressed in the DM+GDF11 group, and the difference was statistically significant (P <0.05).Conclusion Increasing the expression level of GDF11 in vivo can improve aortic vascular injury caused by diabetes mellitus, which is inferred that it may be related to the inhibition of endothelial mesenchymal transition to protect the function of vascular endo-thelial cells and thus improve vascular injury.
