High mobility group box 1 contributes to the endoplasmic reticulum stress of liver in rats with trauma
10.3760/cma.j.issn.2095-4352.2018.04.004
- VernacularTitle:高迁移率族蛋白B1参与介导创伤后大鼠肝组织内质网应激
- Author:
Qingjie ZHANG
1
;
Jianfeng LU
;
Xuehao LI
;
Yichang LIU
;
Guoqing LIU
;
Xinhua HAN
;
Zhenyong GU
Author Information
1. 南通大学医学院法医学系
- Keywords:
High mobility group box 1;
Endoplasmic reticulum stress;
Traumatic stress;
Liver;
Rat
- From:
Chinese Critical Care Medicine
2018;30(4):306-311
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of high mobility group box 1 (HMGB1) in hepatic endoplasmic reticulum stress (ERS) in rats with trauma. Methods Sixty SPF Sprague-Dawley (SD) rats were randomly divided into groups (n = 6). The rat model of liver injury following traumatic stress was established by continuous compressing the bilateral hind-limbs of rats for 3 hours and then intermittent compressing and decompressing for 30 minutes respectively three times with standard weight of 15 kg. The experiment 1 was divided into two groups: control group and 6, 18, 30 hours after crush. The experiment 2 was divided into control group, crush model group (18 hours after crush), HMGB1 inhibitor sodium butyrate (SB) or ethyl pyruvate (EP) groups, and SB or EP treatment groups (500 mg/kg SB solution or 40 mg/kg EP solution was injected intraperitoneally after 3 hours crush). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured with automatic biochemistry analyzer. Histopathological severity of liver injury was assessed by hematoxylin and eosin (HE) staining. The expressions of HMGB1 and ERS-related proteins were detected with Western Blot. The expression and translocation of HMGB1 in liver tissue were evaluated by immuno-histochemical technique. Results ① Compared with the control group, the pathological changes of liver injury, the levels of AST and ALT in serum and protein expression of HMGB1 as well as ERS-related proteins such as glucose regulated protein 78 (GRP78), caspase-12, and inositol-requiring enzyme 1α (IRE1α) in liver tissue were significantly increased after traumatic stress, and reached the peak at 18 hours. The expression of C/EBP-homologous protein (CHOP) was increased in a time-dependent manner and peaked at 30 hours after crush. Immunohistochemistry showed that HMGB1 expression increased at 6 hours after crush, some HMGB1 shifted from nucleus to cytoplasm, and the expression was more obvious at 18 hours. ② Compared with crush model group, the expressions of HMGB1 and ERS-related proteins were significantly decreased following the administration of HMGB1 inhibitors SB or EP (HMGB1/β-actin: 0.703±0.213, 0.512±0.075 vs. 1.041±0.186; GRP78/β-actin:0.614±0.052, 0.450±0.115 vs. 0.847±0.120; caspase-12/β-actin: 0.636±0.066, 0.812±0.142 vs. 1.086±0.130;CHOP/β-actin: 0.314±0.046, 0.621±0.123 vs. 0.996±0.764; IRE1α/β-actin: 0.473±0.033, 0.519±0.094 vs. 0.742±0.054, all P < 0.05), the levels of serum AST and ALT were significantly decreased [AST (U/L): 1 030.50±427.73, 1 414.50±347.86 vs. 2 122.20±322.76; ALT (U/L): 285.75±11.30, 368.50±80.58 vs. 473.80±33.54, all P < 0.01], the degree of acute liver injury was reduced. Only SB or EP could not affect the parameters mentioned above. Conclusion HMGB1-ERS pathway was involved in mediating traumatic stress-induced acute liver injury in rats.
