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PKSI⁃527 对三氯乙烯致敏小鼠体内血浆激肽释放酶⁃激肽系统表达的影响 |
张家祥, 王慧, 许述海, 沈彤, 朱启星
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1. 安徽医科大学公共卫生学院职业卫生与环境卫生系, 安徽合肥 230032; 2. 安徽医科大学附属巢湖医院, 安徽合肥 238000;3. 安徽国际旅行保健中心, 安徽合肥 230000; 4. 安徽医科大学第一附属医院皮肤研究所, 安徽合肥 230032
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摘 要: 目的研究三氯乙烯致敏小鼠体内激肽释放酶-激肽系统(KKS)表达水平,探讨职业性三氯乙烯药疹样皮炎(ODMLT)的发病机制。方法将130只雌性6~8周BALB/c小鼠随机分成空白对照组、溶剂对照组、TCE处理组和TCE+PKSI-527处理组;TCE+PKSI-527处理组在17 d和19 d两次激发前24 h腹腔内注射抑制剂PKSI-527;分别于末次激发后24 h、48 h、72 h和7 d处死动物,造模期间实时记录小鼠体重,计算脏器系数,ELISA法检测血浆前激肽释放酶(PK)、高分子量激肽原(HMWK)和缓激肽(BK)水平。结果 TCE处理组的致敏率为40%,以PKSI-527干预后的致敏率为21.67%,TCE致敏组及TCE+PKSI-527组体重与空白对照组相比均明显减少;TCE处理组小鼠48 h、72 h的肝脏系数明显高于空白对照组,而使用PKSI-527干预后小鼠肾脏系数和脾脏系数均有好转。TCE处理组48 h、72 h时致敏小鼠血浆中PK浓度明显高于溶剂对照组及相应的未致敏组,且在72 h时点达到峰值,使用PKSI-527能够显著降低PK浓度。TCE处理组24 h、48 h致敏小鼠血浆中HMWK浓度明显高于溶剂对照组及相应的未致敏组;TCE+PKSI-527处理组48 h时HMWK浓度明显低于相应时段TCE致敏组。血浆BK的变化特点基本与PK和HMWK表达一致。结论 KKS活化可能参与TCE小鼠致敏及脏器免疫损伤过程。 |
关键词: 三氯乙烯 BALB/ c 小鼠 激肽释放酶⁃激肽系统(KKS) 前激肽释放酶(PK) 高分子量激肽原(HMWK) 缓
激肽(BK) |
中图分类号: R994.3
文献标识码:
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基金项目: 国家自然科学基金资助项目(81502791,81371730); 高等学校博士学科点专项科研基金资助项目(20133420110001); 安徽医科大学科研基金资助项目(2015XKJ005) |
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Effect of PKSI⁃527 on expression of plasma kallikrein⁃kinin system in TCE sensitized mice |
ZHANG Jia⁃xiang, WANG Hui, XV Shu⁃hai, SHEN Tong, ZHU Qi⁃xing
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Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, China
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Abstract: Objective To study the expression level of kallikrein⁃kinin system in trichloroethylene sensitized mice, thereby explore the pathogenesis of occupational dermatitis medicamentosa⁃like of trichloroethylene (ODMLT). Methods 130 female 6~8 weeks old BALB/ c mice were randomly divided into blank control group, solvent control, TCE treatment group and TCE+PKSI⁃527 treatment group; the mice of TCE+PKSI⁃527 treatment group were injected inhibitor PKSI⁃527 24 h earlier before 17 d and 19 d sensitization, respectively. The animals were killed at 24 h, 48 h, 72 h and 7 d respectively after the last injection. Record mice body weight changes and organ coefficients during the period of making model; the levels of lasma PK, HMWK and BK were detected by ELISA assay. Results The study found that the sensitization rate of TCE treatment group was 40%, the rate was only 21 67% after intervention of PKSI⁃527; the body weights of TCE sensitized group and TCE+PKSI⁃527 weight group were all significantly reduced compared with control group; the organ coefficients of liver in TCE treatment group was significantly higher than the control group at 48 h and 72 h of experiment, the PKSI⁃527 intervention might obviously improve kidney and spleen coefficients; plasma PK were significantly higher than solvent control group and corresponding non⁃sensitized group at 48 h and 72 h and the peak was 72 h, PKSI⁃527 could significantly reduce the concentration of PK; plasma HMWK levels of TCE sensitized group were also significantly higher than solvent control group and corresponding non⁃sensitized group at 48 h and 72 h, and
which was significantly lower than that of TCE sensitized group at 48 h; additionally, the changes of plasma BK was also roughly consistent with the expression of PK and HMWK. Conclusion KKS activation may be involved in the processes of sensitization and immunologic organ damage in TCE sensitized mice. |
Keywords: trichloroethylene (TCE) BALB/ c mice kallikrein⁃kinin system (KKS) prekallikrein (PK) high molecular weight kininogen (HMWK) bradykinin (BK) |