ABSTRACT
Objective: To explore the expression of CD55 in liver tissue of trichloroethylene-sensitized mice and discuss the role of CD55 in the liver immune injury of trichloroethylene-sensitized mice. Methods: 6-8 weeks specific pathogen free female BALB/c were randomly divided into blank control group, solvent control group and TCE treatment group to establish BALB/c mice sensitized model. According to mouse skin sensitization reaction score, TCE treatment mice were divided into sensitized and non-sensitized group at 24 h after the last challenge. At 48 h after the last challenge, the blood and aseptic livers were collected. The level of serum ALT was tested by automatic biochemical analyzer and pathology of the liver was observed. C5b-9 deposition was studied by immunohistochemistry (IHC) . CD55 protein expression level in liver tissue was studied by immunohistochemistry and Western blotting. The expression of CD55 mRNA in liver tissue was detected by qRT-PCR. Results: Liver function test result showed level of serum ALT in TCE sensitized group was significantly higher than solvent control group and TCE non-sensitized group (P<0.05) . There was ballooning degeneration and necrosis of liver cells in TCE sensitized group. IHC demonstrated that TCE sensitized group had obviously increased content of C5b-9 but had reduced content of CD55 compared with solvent control group and TCE non-sensitized group (P<0.05) . Western blotting also showed that TCE sensitized group had lower expression of CD55 than solvent control group and TCE non-sensitized group (P<0.05) . qRT-PCR showed that CD55 mRNA expression level in liver tissue of TCE sensitized group was apparently lower than solvent control group and TCE non-sensitized group (P<0.05) . Conclusion: Complement activation may be involved in TCE-induced liver injury, and the expression change of complement regulatory protein CD55 may play essential role in the process.
Subject(s)
Complement System Proteins/metabolism , Immunologic Factors/metabolism , Liver/physiopathology , Trichloroethylene/toxicity , Animals , Chemical and Drug Induced Liver Injury , Female , Mice , Mice, Inbred BALB C , Solvents/toxicityABSTRACT
Objective: To explore the effect of complement C3 a-C3a receptor in the kidney immune inju-ry in trichloroethylene-sensitized mice by using C3a receptor specific antagonist C3aRA and discuss the patho-genesis of kidney injury in occupational dermatitis medicamentosa-like of trichloroethylene (ODMLT) . Methods: 42 female 6~8 weeks old BALB/c mice of specific pathogen free were randomly divided into blank control group (5) , solvent control group (5) , TCE treatment group (16) and TCE+C3aRA treatment group (16) . The TCE treat-ment group and TCE+C3aRA treatment group were further divided into the sensitized group and the non-sensi-tized group according to the skin sensitization test score. Renal function was detected by biochemical detection kit; expression of C3aR in kidney tissue was detected by qPCR; expression of IL-1ß and TNF-α protein were de-tected by immunohistochemical. Results: Compared with solvent control group and corresponding non-sensitized group, CRE and BUN in TCE sensitized group and TCE + C3aRA sensitized group were significantly increased (P<0.05) . Compared with TCE sensitized group, CRE and BUN in TCE+C3aRA sensitized group were signifi-cantly decreased (P<0.05) . Compared with solvent control group and TCE non-sensitized group, the expression level of C3aR gene in kidney tissue in TCE sensitized group was significantly increased (P<0.05) . There was a large number of IL-1ß and TNF-α protein expression in kidney tissue in TCE sensitized group and TCE+C3aRA sensitized group. Compared with the TCE sensitized group, the expression level of IL-1ß and TNF-α protein in kidney tissue in TCE+C3aRA sensitized group was significantly decreased (P<0.05) . Conclusion: C3a-C3aR may be involved in the kidney immune injury in TCE sensitized mice, C3aRA has a protective effect on the kid-ney immune injury in TCE sensitized mice.
Subject(s)
Complement C3a/metabolism , Kidney/pathology , Receptors, Complement/metabolism , Trichloroethylene/toxicity , Animals , Female , Kidney/drug effects , Kidney/metabolism , Mice , Mice, Inbred BALB C , Receptors, Complement/antagonists & inhibitorsABSTRACT
OBJECTIVE: Through testing the expression of complement C3 fragment C3b and iC3b, C5b-9 as well as indexes of KKS before and after using kallikrein-kinin system inhibitor PKSI-527, observing the relevant between KKS and complement system, we preliminary study on the mechanism how KKS works on the renal injury of sensitized mice model induced by trichloroethylene. METHODS: Female BALB/c mice (6~8 weeks) were randomly divided into blank control group (5), TCE treated group (15), PKSI-527+TCE treated group (15). Mice were sensitized with TCE in the 1,3,7,10 days, the first and the last challenge were on day 17 and 19. 24h before every challenge, mice in PKSI-527+TCE group were treated with intraperitoneal injection of KKS inhibitor PKSI-527 inhibitor (50mg/kg). Mice were killed 72h after the last challenge. The function of kidney in mice were detected and kidney B1R, B2R expression were detected using real-time quantitative PCR, mice kidney complement C3 fragments C3b, iC3b and C5b-9 deposition were also detected by chemoimmunology. RESULTS: Compared with blank control group, all indexes expressions in the solvent control group have no significant change. Compared with the solvent control group, BUNãCr level and B1RãB2R level have an significant increase (P< 0.05) in TCE sensitized group and PKSI-527+TCE sensitized group; There is a sharp decrease in PKSI-527+TCE sensitized group compared to TCE sensitized group(P< 0.05). CONCLUSION: The renal damage in the TCE sensitization mouse model may aggravated by upregulate complement system followed by the activation of kallikrein-kinin system.
