RNAi沉默TREM-1对白假丝酵母感染脓毒症大鼠多器官损害的机制

Mechanism of RNAi silencing TREM-1 on multiple organ damage in septic rats infected with Candida albicans

目的研究RNA干扰(RNAi)沉默髓系细胞触发受体-1(TREM-1)对白假丝酵母感染脓毒症大鼠多器官损害的相关作用机制。方法选取40只清洁级SD雄性大鼠,随机选取10只分为正常组,其余30只建立白假丝酵母感染导致的脓毒症模型,成功27只,分为模型组、对照组、TREM-1沉默组,各9只。检测天冬氨酸转氨酶(AST)、尿素氮(BUN)、丙氨酸转氨酶(ALT)、肌酐(Cr)、髓过氧化物酶(MPO)、二胺氧化酶(DAO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6、超氧化物歧化酶(SOD)和丙二醛(MDA)、pDAP12、核因子-кB (NF-кB)p65、抑制性核转录因子结合蛋白α(IкBα)蛋白表达。结果 TREM-1沉默组ALT、AST、Cr、MPO、MDA、TNF-α、IL-1β、IL-6水平低于模型组和对照组,DAO、SOD水平高于对照组和模型组(P<0.05)。TREM-1沉默组pDAP12、NF-кB p65蛋白表达低于模型组和对照组,IкBα蛋白表达高于模型组和对照组(P<0.05)。结论RNAi沉默TREM-1通过阻断TREM-1信号通路,抑制TNF-α、IL-1β、IL-6水平,从而改善白假丝酵母感染脓毒症模型大鼠多器官损伤状况。

OBJECTIVE To investigate the mechanism of silencing triggering receptor expressed on myeloid cells-1(TREM-1) by RNA interference(RNAi) on multiple organ damage in septic rats infected with Candida albicans.METHODS Totally 40 clean grade SD male rats were selected and 10 rats were randomly selected and divided them into normal group,the remaining 30 rats were infected with C.albicans to establish the sepsis model,of which 27 successful infection rats were divided into model group,control group and TREM-1 silence group,with 9 rats in each group.Aspartate aminotransferase(AST),urea nitrogen(BUN),alanine aminotransferase(ALT),creatinine(CR),myeloperoxidase(MPO),diamine oxidase(DAO),tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),interleukin-6(IL-6),superoxide dismutase(SOD),malondialdehyde(MDA),pdap12,NF-к B P65,and protein expression of inhibitory nuclear factor binding protein α(I к B α) were detected.RESULTS The levels of alt,AST,Cr,MPO,MDA,TNF-α,IL-1 β and IL-6 in the TREM-1 silencing group were signigifcantly lower than those in model group and control group,while the DAO and SOD levels were signigifcantly higher than those in control group and model group(P<0.05).The expression of pdap12 and NF-кB p65 protein in TREM-1 silencing group was lower than those in model group and control group,while the I к B α protein expression was signigifcantly higher than that in model group and control group(P<0.05).CONCLUSION RNAi silencing TREM-1 could inhibit the levels of TNF-α,IL-1 β and IL-6 by blocking the TREM-1 signaling pathway,thereby improving the multiple organ injury in septic rats infected by C.albicans.