Effect of ulinastatin pretreatment on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats with major hepatectomy and ischemia-reperfusion injury.
- Author:
Yulin ZHU
1
;
Rongsheng ZHOU
;
Hui YANG
;
Jing TAN
;
Xiaoqi ZHANG
;
Qining LIU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Proliferation; Cyclin D1; metabolism; Cyclin-Dependent Kinase 4; metabolism; Glycoproteins; pharmacology; Hepatectomy; adverse effects; Hepatocytes; cytology; drug effects; Interleukin-6; metabolism; Liver; blood supply; Liver Regeneration; drug effects; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; etiology; metabolism; STAT3 Transcription Factor; metabolism; Signal Transduction; drug effects; Tumor Necrosis Factor-alpha; metabolism
- From: Journal of Southern Medical University 2012;32(9):1301-1306
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of pretreatment with ulinastatin on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats after 70% hepatectomy combined with ischemia-reperfusion injury.
METHODSA total of 120 normal male SD rats weighing 230-280 g were randomized into 3 groups (n=40), namely simple partial hepatectomy (PH) group, partial hepatectomy with ischemia-reperfusion (PHIR) group, and ulinastatin group. All the rats received resection of the left and middle liver lobes. In PHIR group, the remnant right lobes were subjected to blood flow occlusion for 30 min; in UTI group, the rats were given 50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant liver tissues were examined for regenerated liver weight, PCNA staining, TNF-α and IL-6, STAT-3, cyclin D1, and Cdk4 expressions.
RESULTSThe regenerated liver weight and PCNA positivity rates were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h after the reperfusion (P<0.05). In ulinastatin group, the levels of TNF-α and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1 and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h (P<0.05).
CONCLUSIONUlinastatin can promote liver regeneration after major hepatectomy and ischemia-reperfusion injury, and the effect is possibly related with activation of IL-6/STAT-3 signal pathway, which promotes the synthesis of cyclin Dl-Cdk4 complex and hepatocyte proliferation.