Protective effect of adeno-associated virus sense transfection ofGDFll on vascular injury in type 2 diabetic rats
10.19405/j.cnki.issn1000-1492.2024.05.013
- Author:
Yuqin Wang
1
,
2
;
Shaoqing Cao
1
,
2
;
Zhangyu Wang
1
,
2
;
Chengsi Li
1
,
2
;
Jiangping Ye
1
,
2
;
Gangjun Zong
1
,
2
Author Information
1. Dept of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214000
2. Dept of Cardiovascular Medicine, The Fih Clinical College, Anhui Medical University,Hefei 230000
- Publication Type:Journal Article
- Keywords:
diabetes mellitus;
adeno-associated virus;
recombinant growth transforming factor 1l;
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 adenoassociated virus sense transfection up-regulating the expressionlevel 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 usinghigh -sugar and high-fat chow plus small-dose streptozotocin (STZ) combined induction. Both normal rats and diabetic model rats were randomly divided into five groups: blank control group ( Control group) , negative virus control group ( NC group), GDF11 adeno-associated virus group ( GDFl1 group), diabetic group ( DM group), anddiabetic + GDF11 adeno-associated virus group ( DM + GDFl1 group). After 8 weeks of feeding, the serum con-centrations of insulin ( INS ), advanced glyeosylation end products ( AGES), recombinant growth transforming fac.tor 11 ( GDF11 ), total cholesterol (T-CH0 ), triglycerides (TG), low-density lipoproteins (LDL-C), high-density lipoproteins ( HDL-C), asymmetric dimethylarginine ( ADMA), and malondialdehyde ( MDA) were assayed inthe rats ; periodic acid-schiff stain( PAS stain) was used to observe the sites of glycogen deposition, and hematoxylin-eosin staining ( HE) was used to observe vascular damage. Scanning electron microscopy was used to observethe damage of vascular endothelial cells and vascular elastic fibers, and protein blotting and immunohistochemistrwere used to detect the expression levels of vascular injury-related proteins. Protein blotting and immunohistochemistry were used to detect the expression levels of vascular injury-related proteins.
Results:The biochemical indexes showed that the serum concentrations of AGES, T-CHO, TG, LDL-C and MDA were higher in the DM groupthan 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 AGE'S and HDL-C were not sig.nificantly lower in the DM + GDF1l group compared with the DM group ( P <0. 05). HDL-C was not significantlydilerent from the DM group, and several other data were improved ( P<0. 05 ). Pathological staining suggestedthat 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 brokeolf in an irregular alignment , and electron microscopy observed endothelial damage in the vasculature and elastic fibers broke off in the DM group, and these changes attenuated in the DM + GDFl1 group. Protein blotting and im.munohistochemistry indicated that the expression of endothelial cell-associated proteins decreased in the DM groug( P <0. 05), and mesenchymal markers elevated in the DM group ( P <0. 05 ), these proteins were regressed inthe DM + GDFl1 group, and the difference was statistically significant (P<0.05).
Conclusion:Inereasing theexpression level of GDFl1 in vivo can improve aortic vascular injury caused by diabetes mellitus, which is inferredthat 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.
- Full text:2024072815405639927腺相关病毒感染GDF11对...尿病大鼠血管损伤的保护作用_王玉琴.pdf
