Role ofdenervation on kidney tubulointerstitial fibrosis induced by ischemia reperfusion injury via Nrf2/TGF-β pathway
10.3760/cma.j.cn421203-20220505-00096
- VernacularTitle:Nrf2/TGF－β通路在肾小管间质纤维化中的作用及机制
- Author:
Qian SUN
1
;
Yifei WANG
;
Qiao TANG
;
Cheng ZENG
;
Chong DONG
Author Information
1. 武汉大学人民医院麻醉科，武汉 430060
- Keywords:
Kidney transplantation;
Mice;
Transforming growth factor;
Ischemia reperfusion injury
- From:
Chinese Journal of Organ Transplantation
2022;43(9):544-550
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of denervation on kidney tubulointerstitial fibrosis(TIF)induced by ischemia reperfusion injury(IRI)via NF-E2-related factor-2 (Nrf2)/transforming growth factor-β(TGF-β)pathway in mice.Methods:C57BL/6 mice were randomized into four groups(n=12 each)of sham, kidney ischemia reperfusion(IR), RDN and RDN+ IR(DIR). At Days 1 and 7 post-reperfusion, kidney histology and fibrotic injury are observed after hematoxylin-eosin(HE)and Masson staining.α-SMA protein is detected by immunohistochemistry.The serum levels of blood urea nitrogen(BUN), creatinine(Cr)and neutrophil gelatinase-associated lipocalin(NGAL)are measured.And the contents of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 4(IL-4), interleukin 10(IL-10)and interleukin 13(IL-13)in kidney tissues are detected.Western blot is utilized for observing the expression levels of Nrf2, TGF-β and phospho-Smad3 protein in kidney tissues.Results:Compared with sham group, kidney histologic score, serum levels of BUN, Cr and NGAL and contents of MDA, IL-4, IL-10 and IL-13 in kidney tissues spiked while activity of SOD declined.Protein expressions of Nrf2, TGF-β and phospho-Smad3 rise in IR-1 and DIR-1 groups( P<0.05). Compared with IR-7 group, degree of fibrosis and levels of α-SMA, IL-4, IL-10 and IL-13 drop in DIR-7 group, Nrf2 protein expression increased and protein expressions of TGF-β and phospho-Smad3 decreased( P<0.05). Conclusions:Acute oxidative stress injury induced by IRI becomes aggravated after kidney denervation and initiates TIF.The long-term expression of TGF-β and phosphorylation of Smad3 are suppressed due to a continuous activation of Nrf2 pathway, thereby blunting the long-term TIF degree of kidney.
