Mechanism of long non-coding RNA FUT8-AS1 regulating growth differentiation factor 15 on diabetic cerebral ischemia-reperfusion injury
10.3969/j.issn.1006-6187.2025.10.009
- VernacularTitle:长链非编码RNA FUT8-AS1通过调控生长分化因子15影响糖尿病性脑缺血再灌注损伤机制的研究
- Author:
Xiaofeng LIU
1
;
Tingting WANG
;
Zhe SONG
;
Qian GU
;
Chunwang SONG
Author Information
1. 050000 石家庄市人民医院神经内科
- Publication Type:Journal Article
- Keywords:
Long non-coding RNA FUT8-AS1;
Growth differentiation factor 15;
Diabetes mellitus;
Cerebral ischemia-reperfusion injury
- From:
Chinese Journal of Diabetes
2025;33(10):768-779
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of long non-coding RNA(LncRNA)FUT8-AS1 on diabetic ischemia-reperfusion injury by regulating growth differentiation factor 15(GDF15).Methods Male SD rats were randomly divided into Sham group,cerebral ischemia-reperfusion injury(MCAO/R)group,diabetic cerebral ischemia-reperfusion injury(DM-MCAO/R)group,DM-MCAO/R+sh NC group,and DM-MCAO/R+sh FUT8-AS1 group.TTC staining was used to assess the size of cerebral infarction.Tunel staining was selected to evaluate the apoptosis of neurons in brain tissue.Nissl staining was used to assess the number of neurons in brain tissue.The expression of LncRNA FUT8-AS1,GDF15 mRNA in Willis arterial loop and internal carotid artery tissues were detected by qRT-PCR.The expression of α-SMA,eNOS,p-eNOS,GDF15 protein in Willis arterial loop and internal carotid artery was detected by Western blot.The rat brain microvascular endothelial cells were divided into control(Con)group,OGD/R group,HG-OGD/R group,HG-OGD/R+sh NC group,HG-OGD/R+sh FUT8-AS1 group,HG-OGD/R+sh FUT8-AS1+oe NC group,and HG-OGD/R+sh FUT8-AS1+oe GDF15 group.MTT assay was used to detect cell viability.Lactate dehydrogenase(LDH)assay was used to detect cell damage.The expression ofα-smooth muscle actin(α-SMA),endothelial nitric oxide synthase(eNOS),p-eNOS protein was detected by Western blot.Results Compared with the Sham group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased,the morphology was shrunk,and the color was dark in the MCAO/R group.Compared with the MCAO/R group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the DM-MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased in the DM-MCAO/R group.Compared with the DM-MCAO/R+sh NC group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein decreased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins increased in the DM-MCAO/R+sh FUT8-AS1 group(P<0.05),and the number of neurons in the hippocampus increased in the DM-MCAO/R+sh FUT8-AS1 group.Compared with the Con group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the OGD/R group(P<0.05).Compared with the OGD/R group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the HG-OGD/R group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression decreased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions increased in the HG-OGD/R+sh FUT8-AS1 group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity decreased in the HG-OGD/R+oe GDF15 group(P<0.05).Compared with the HG-OGD/R+sh FUT8-AS1+oe NC group,the expression of α-SMA,eNOS,p-eNOS proteins decreased in the HG-OGD/R+sh FUT8-AS1+oe GDF15 group(P<0.05).Conclusions LncRNA FUT8-AS1 may exacerbate diabetic cerebral ischemia-reperfusion injury by regulating GDF15.
