激肽释放酶激肽系统活化在三氯乙烯致敏小鼠肾脏损伤中的作用  

Role of kallikrein kinin system activation in kidney injury induced by trichloroethylene sensitized mice

作　　者：刘敏[1] 张澄[1] 杨鹏[1] 黄建[1] 臧丹丹[1] 张家祥[1] 朱启星 

机构地区：[1]安徽医科大学公共卫生学院职业卫生与环境卫生学系,合肥230032 [2]第一附属医院皮肤研究所

出　　处：《中华劳动卫生职业病杂志》2016年第3期184-188,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金项目（81371730,81502791）;高等学校博士学科点专项科研基金（20133420110001）

摘　　要：目的观察使用血浆激肽释放酶激肽系统（kallikrein—kinin system，KKS）抑制剂前后，小鼠血浆中补体C3片段C3b，iC3b，C5b-9蛋白沉积与血浆KKS系统指标的相关性，探讨KKS在三氯乙烯（triehloroethylene，TCE）致敏小鼠肾脏损伤中的作用。方法将雌性BALB／c小鼠（6-8周）随机分为空白对照组（5只）、溶剂对照组（5只）、TCE处理组（15只）、PKSI-527＋TCE处理组（15只），在实验第1、3、7、10天进行致敏处理，第17、19天进行首次和末次激发，每次激发前24h对TCE＋PKSI-527处理组的小鼠腹腔注射KKS抑制剂PKSI-527（50mg／kg）。末次激发72h后，检测小鼠肾脏功能；实时定量PCR检测各组小鼠肾脏中B1R，B2R mRNA表达；免疫组化检测各组小鼠肾脏补体C3片段C3b，iC3b，C5b-9蛋白沉积。结果与溶剂对照组比较，TCE致敏组及TCE＋PKSI-527致敏组血清中BUN、Cr水平及B1R、B2R mRNA表达均明显升高，差异均有统计学意义（P〈0．05）；TCE致敏组及TCE＋PKSI-527致敏组补体C3片段C3b，iC3b，C5b-9蛋白沉积明显升高；与TCE致敏组比较，TCE＋PKSI-527致敏组血清中BUN、Cr水平及B1R、B2R mRNA表达明显降低，差异均有统计学意义（P〈0.05）；TCE＋PKSI-527致敏组补体C3片段C3b、iC3b、C5b-9蛋白沉积降低。结论KKS系统激活可能是通过上调补体系统参与了TCE致敏小鼠肾脏损伤过程。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, BUN,Cr level and BIR,B2R 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.

关 键 词：三氯乙烯 激肽释放酶激肽系统 补体 血尿素氮 

分 类 号：R135[医药卫生—劳动卫生]