A Novel Dorsal Slit Approached Non-Ischemic Partial Nephrectomy Method for a Renal Tissue Regeneration in a Mouse Model.
10.1007/s13770-018-0123-0
- Author:
So Young CHUN
1
;
Dae Hwan KIM
;
Jeong Shik KIM
;
Hyun Tae KIM
;
Eun Sang YOO
;
Jae Wook CHUNG
;
Yun Sok HA
;
Phil Hyun SONG
;
Yoon Ki JOUNG
;
Dong Keun HAN
;
Sung Kwang CHUNG
;
Bum Soo KIM
;
Tae Gyun KWON
Author Information
1. BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, South Korea.
- Publication Type:Original Article
- Keywords:
Ischemia-reperfusion;
Renal regeneration;
Inflammation;
Apoptosis;
Fibrosis
- MeSH:
Animals;
Apoptosis;
Blood Urea Nitrogen;
Cell Count;
Cell Movement;
Chemistry;
Creatinine;
Cytokines;
DNA Nucleotidylexotransferase;
Epithelial Cells;
Fibrosis;
Immunohistochemistry;
Inflammation;
Kidney;
Laparotomy;
Methods*;
Mice*;
Nephrectomy*;
Real-Time Polymerase Chain Reaction;
Regeneration*
- From:
Tissue Engineering and Regenerative Medicine
2018;15(4):453-466
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Kidney ischemia-reperfusion (IR) via laparotomy is a conventional method for kidney surgery in a mouse model. However, IR, an invasive procedure, can cause serious acute and chronic complications through apoptotic and inflammatory pathways. To avoid these adverse responses, a Non-IR and dorsal slit approach was designed for kidney surgery. METHODS: Animals were divided into three groups, 1) sham-operated control; 2) IR, Kidney IR via laparotomy; and 3) Non-IR, Non-IR and dorsal slit. The effects of Non-IR method on renal surgery outcomes were verified with respect to animal viability, renal function, apoptosis, inflammation, fibrosis, renal regeneration, and systemic response using histology, immunohistochemistry, real-time polymerase chain reaction, serum chemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Masson's trichrome staining. RESULTS: The Non-IR group showed 100% viability with mild elevation of serum blood urea nitrogen and creatinine values at day 1 after surgery, whereas the IR group showed 20% viability and lethal functional abnormality. Histologically, renal tubule epithelial cell injury was evident on day 1 in the IR group, and cellular apoptosis enhanced TUNEL-positive cell number and Fas/caspase-3 and KIM-1/NGAL expression. Inflammation and fibrosis were high in the IR group, with enhanced CD4/CD8-positive T cell infiltration, inflammatory cytokine secretion, and Masson's trichrome stain-positive cell numbers. The Non-IR group showed a suitable microenvironment for renal regeneration with enhanced host cell migration, reduced immune cell influx, and increased expression of renal differentiation-related genes and anti-inflammatory cytokines. The local renal IR influenced distal organ apoptosis and inflammation by releasing circulating pro-inflammatory cytokines. CONCLUSION: The Non-IR and dorsal slit method for kidney surgery in a mouse model can be an alternative surgical approach for researchers without adverse reactions such as apoptosis, inflammation, fibrosis, functional impairment, and systemic reactions.