Protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis on sepsis-associated acute kidney injury in mice
10.16250/j.32.1374.2020122
- VernacularTitle:旋毛虫重组成虫丝氨酸蛋白酶抑制剂对小鼠脓毒症急性肾损伤的保护作用
- Author:
Hui-Juan YANG
1
,
2
;
Hui-Hui LI
3
,
4
;
Xue-Rui PANG
3
;
Shi-Fang GAO
3
;
Jin-Bao LIANG
3
;
Xin ZHENG
3
;
Ding-Ru LI
3
;
Yu-Hang WANG
3
;
Xue-Qin YU
3
;
Xue-Qian QIAN
3
;
Xiao-Di YANG
3
,
4
;
Wei-Dong CHEN
1
Author Information
1. Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
2. Anhui Provincial Key Laboratory of Infection and Immunity, China
3. Anhui Provincial Key Laboratory of Infection and Immunity, China
4. Department of Basic Medicine, Bengbu Medical College, China
- Publication Type:Journal Article
- Keywords:
Trichinella spiralis;
Serine protease inhibitor;
Sepsis;
Acute kidney injury;
Myeloid differentiation factor 88;
nuclear factor kappa-B
- From:
Chinese Journal of Schistosomiasis Control
2020;32(4):361-366
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. Methods A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 μL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 μL) containing TsadSPI (2 μg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. Results At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-β levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-β levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. Conclusions TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.
