一种用于小鼠模型肾组织再生的新型经背侧切口非缺血性部分肾切除术方法。
A Novel Dorsal Slit Approached Non-Ischemic Partial Nephrectomy Method for a Renal Tissue Regeneration in a Mouse Model.
作者信息
Chun So Young, Kim Dae Hwan, Kim Jeong Shik, Kim Hyun Tae, Yoo Eun Sang, Chung Jae-Wook, Ha Yun-Sok, Song Phil Hyun, Joung Yoon Ki, Han Dong Keun, Chung Sung Kwang, Kim Bum Soo, Kwon Tae Gyun
机构信息
1BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 South Korea.
2Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 Hyunchung-ro, Nam-gu, Daegu, 42415 South Korea.
出版信息
Tissue Eng Regen Med. 2018 Jun 1;15(4):453-466. doi: 10.1007/s13770-018-0123-0. eCollection 2018 Aug.
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.
背景
通过剖腹术进行肾脏缺血再灌注（IR）是小鼠模型肾脏手术的传统方法。然而，IR作为一种侵入性操作，可通过凋亡和炎症途径导致严重的急性和慢性并发症。为避免这些不良反应，设计了一种非IR和背侧切开法用于肾脏手术。
方法
将动物分为三组，1）假手术对照组；2）IR组，通过剖腹术进行肾脏IR；3）非IR组，非IR和背侧切开法。使用组织学、免疫组织化学、实时聚合酶链反应、血清化学、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色和Masson三色染色，从动物存活率、肾功能、凋亡、炎症、纤维化、肾脏再生和全身反应方面验证非IR方法对肾脏手术结果的影响。
结果
非IR组术后第1天存活率为100%，血清尿素氮和肌酐值轻度升高，而IR组存活率为20%，且出现致命的功能异常。组织学上，IR组术后第1天肾小管上皮细胞损伤明显，细胞凋亡增加了TUNEL阳性细胞数量以及Fas/caspase-3和KIM-1/NGAL表达。IR组炎症和纤维化程度较高，CD4/CD8阳性T细胞浸润、炎性细胞因子分泌增加，Masson三色染色阳性细胞数量增多。非IR组显示出适合肾脏再生的微环境，宿主细胞迁移增强，免疫细胞流入减少，肾脏分化相关基因和抗炎细胞因子表达增加。局部肾脏IR通过释放循环促炎细胞因子影响远端器官的凋亡和炎症。
结论
小鼠模型肾脏手术的非IR和背侧切开法可为研究人员提供一种替代手术方法，且无凋亡、炎症、纤维化、功能损害和全身反应等不良反应。
Zotero 插件